Exploring the Therapeutic Potential of Momordica charantia in Targeting Protein Kinase C Delta (PRKCD) for Type 2 Diabetes Mellitus: Insights from Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations 

Exploring the Therapeutic Potential of Momordica charantia in Targeting Protein Kinase C Delta (PRKCD) for Type 2 Diabetes Mellitus: Insights from Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exploring the Therapeutic Potential of Momordica charantia in Targeting Protein Kinase C Delta (PRKCD) for Type 2 Diabetes Mellitus: Insights from Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations Ruchi Yadav, Nidhi Nambiar, Manushi Shah, Bhumika Patel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5948998/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Jul, 2025 Read the published version in In Silico Pharmacology → Version 1 posted 11 You are reading this latest preprint version Abstract Type 2 diabetes mellitus (T2DM) is a chronic condition caused by decreased insulin production and increased insulin resistance, and its prevalence has increased by 49% since 1990. Current treatments for T2DM include pharmacological agents and lifestyle modifications, but they are limited by their side effects and cost. Herbal remedies and natural products have become popular alternative treatments for T2DM as they are associated with fewer side effects. Momordica charantia Linn. (bitter melon) is a member of the Cucurbitaceae family and has been used as a traditional anti-diabetic remedy in various countries for many years. The plant contains several biologically active compounds, including glycosides, saponins, alkaloids, triterpenes, proteins, and steroids. The hypoglycemic activity of Momordica charantia is primarily attributed to its saponins, which are collectively known as charantins, and alkaloids. Through network pharmacology, Molecular docking and MD simulation we found underlying, mechanism of karela in the treatment of T2DM. Through network pharmacology from 49 targets we found the Protein kinase C delta (PRKCD) as a hub gene. Various studies have also indicated the pathophysiological role of PRKCD in the development of T2DM. Gene expression analysis in 24 patients revealed an overexpression of PRKCD in both prediabetic and diabetic patients. Molecular docking data identified the top three active constituents of karela as Momordicoside C, Momorcharaside B, and Momordin I, with docking scores of -8.0 kcal/mol, -7.9 kcal/mol, and − 7.9 kcal/mol, respectively. Additionally,MD simulation was performed using the GROMACS software and we found that Momordicoside C and Momorcharaside B has good stability and also formed the H-bond at end of the 100ns of simulation. This study revelled new mechanism action of a well-known plant karela in the treatment of T2DM. T2DM PRKCD Karela Momordicoside C Momorcharaside B Network Pharmacology Molecular Docking MD Simulation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 1. Introduction Diabetes mellitus is a serious metabolic disease that affects human health. There are three types of diabetes: type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) [ 1 , 2 ]. T2DM is a chronic condition caused by decreased insulin production and increased insulin resistance and is prevalent worldwide, with a 49% increase since 1990. In 2019, there were 437.9 million reported cases of T2DM, primarily in low- and middle-income countries [ 3 ]. T2DM is associated with metabolic diseases such as obesity and increases the risk of heart disease, which is the leading cause of death globally[ 4 ]. Currently, mainstream treatments for T2DM include pharmacological agents and lifestyle modification, but these are limited by side effects and cost [ 5 ]. Natural products, such as herbal remedies, have become an increasingly popular alternative treatment for T2DM as they have fewer side effects and low cost. The use of natural substances for the treatment of diabetes is considered a promising strategy that may provide solutions for the limitations of current treatments [ 6 , 7 ]. Plants and their products play a crucial role in nutrition by providing essential nutrients and aiding in the prevention of various illnesses, ultimately enhancing the quality of life worldwide. Traditional plant-based medicines have been used for centuries, but it is important to standardize them to evaluate their potential benefits [ 8 ]. The Momordica charantia is widely popular plant in India. Commonly it is known as “bitter melon” and in Hindi as “karela”. This plant belongs to family Cucurbitaceae [ 9 ]. Traditionally, bitter melon has been known for its potent antidiabetic, anticancer, anti-inflammatory, antiviral and cholesterol-lowering medicinal properties [ 10 , 11 ]. The plant contains several biologically active compounds, including glycosides, saponins, alkaloids, triterpenes, proteins, and steroids. The hypoglycemic activity of Momordica charantia is primarily attributed to its saponins, collectively known as charantins, and alkaloids. These saponins have been shown to lower blood glucose levels in both animal studies and clinical trials. Additionally, several phytochemicals isolated from the plant, such as charantins, polypeptide-p, momordin Ic, oleanolic acid 3-O-monodesmoside, and oleanolic acid 3-O-glucuronide, have been found to exhibit hypoglycemic activity. These compounds enhance insulin secretion, increase glucose uptake, and reduce glucose production in the liver. Overall, the presence of various bioactive compounds in Momordica charantia makes it a promising natural remedy for diabetes management [ 12 , 13 ]. However, due to the presence of multiple compounds and multiple targets in Karela, its underlying mechanism has not been thoroughly explored. In present study we explored the anti-diabetic mechanism of this plant by using a network pharmacology study and validated through molecular docking and molecular dynamic (MD) simulation study. The network pharmacology study is emerging computational technique for drug discovery and development. Initially, the bioactive compounds of Karela were screened, and the overlapping targets between Karela and T2DM were identified. Protein-protein interaction (PPI) networks and core targets were then established through network topological structure analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to determine the functions and pathways associated with the overlapping targets. Lastly, molecular docking and molecular dynamic (MD) simulations were performed to evaluate the compound-target binding affinity based on the network pharmacology results. The study outcome aids the identification of novel possible targets of plant constituents and enrichment pathways against T2DM. 2. Material and Methods 2.1 Network Pharmacology 2.1.1 Compound mining and target predictions of active constituents of karela Active compounds from Momordica charantia L. were chosen by conducting a literature survey, and their SMILES were subsequently downloaded using PubChem ( https://pubchem.ncbi.nlm.nih.gov/ ). BindingDB [ 14 ] ( https://www.bindingdb.org/rwd/bind/index.jsp ) and SwissTargetPrediction (STP) [ 15 ] ( https://www.swisstargetprediction.ch/ ) were explored against these active compounds to predict their respective target genes focusing on a " homo sapiens " keyword. 2.1.2 Collection of T2DM targets T2DM related targets were searched using keywords’ “diabetes”, “diabetes mellitus”, type 2 diabetes mellitus”, “insulin-independent diabetes”, “diabetes mellitus type 2” in databases such as DisGeNET ( https://disgenet.com/ ) [ 16 ], Therapeutic Target Database ( https://db.idrblab.net/ttd/ ) [ 17 ] and Open Target ( https://www.opentargets.org/ ) [ 18 ]. The target names were matched to their corresponding UniProt IDs ( https://www.uniprot.org/ ) [ 19 ]. Venny 2.1 ( https://bioinfogp.cnb.csic.es/tools/venny/ ) [ 20 ] was utilized to identify overlapping targets from all three databases. The common targets of T2DM, retrieved from three databases, and the identified targets of active compounds of Karela, obtained from SwissTargetPrediction and BindingDB databases, were uploaded into Venny 2.1 to create a Venn diagram showing the overlap between T2DM targets and the targets of Karela's active constituents. The intersection of targets from this Venn diagram was then used for further studies. 2.1.3 PPI Network of Intersected Gene To further investigate the mechanism of action of active constituents of karela in the treatment of T2DM, the intersection of 49 targets was imported into String. Protein-protein interactions were analysed using String ver. 11.0 ( https://string‐db.org/ ) [ 21 ]. The minimum combined score was set to 0.9 and protein-protein‐interaction (PPI) relationships for “ Homo sapiens” were obtained. Targets without interaction were removed and the data were saved as SIF files. Next, the PPI network was constructed by importing node1 and node2 into Cytoscape [ 22 ]. Finally, the core targets were screened by cluster analysis using the MCODE [ 23 ], CytoHubba [ 24 ] and CytoNCA [ 25 ] plugin of Cytoscape. 2.1.4 GO and KEGG Enrichment Analysis The GO enrichment analysis was conducted through the utilization of the DAVID (Database for Annotation, Visualization and Integrated Discovery) ( https://david.ncifcrf.gov/tools.jsp ) database [ 26 ]. The Biological Process (BP), Cellular Component (CC), and Molecular Function (MF) modules were chosen and significant biological annotations (p < 0.05) were selected for analysis. Additionally, KEGG pathway [ 27 ] enrichment analysis was conducted to identify the principal signaling pathways involved in T2DM using the DAVID database and the graph for KEGG and GO plotted by using SRPLOT( https://bioinformatics.com.cn/en ) [ 28 ]. 2.1.5 Different Gene Expression Analysis Through network analysis of 49 predicted targets, Protein Kinase C Delta Type (PRKCD) was identified as a hub gene. To determine whether this target is involved in the pathophysiology of T2DM, gene expression analysis was performed using the GEO database. In this database, term “PRKCD” was searched along with “ Homo sapiens” as filer under species tab. The GSE26168 dataset ( https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE26168&platform=GPL6883 ) was selected, and GEO2R analysis was performed to download the data. This study involved 24 participants, including 8 controls, 7 with impaired fasting glucose, and 9 with T2DM. PRKCD levels in the blood were analyzed in these groups. 2.2 Prediction of Binding Pocket In this study, PRKCD was identified as a hub gene through network analysis. However, it does not have a native ligand in the PDB. Therefore, prior to molecular docking, the binding pockets were identified using the CastpFold server ( https://cfold.bme.uic.edu/castpfold/ ), which provides detailed information on the topological and geometrical features, as well as pocket details, of the uploaded protein [ 29 ]. Additionally, the PocketDepth server ( http://proline.physics.iisc.ernet.in/pocketdepth/ ), a computational tool for identifying binding pockets in protein structures, was utilized [ 30 ]. 2.3 Molecular Docking Molecular docking is a computational method used to study the interactions between a protein and a ligand [ 31 ]. Initially, all compounds of Karela were searched for in the PubChem database, and the structures were exported in 3D ‘mol2’ format. Subsequently, the 3D structure of the core protein Protein Kinase C Delta Type (PRKCD) (PDB ID: 1YRK, 1.7Å) was downloaded from the Protein Data Bank ( https://www.rcsb.org/ ). The processes of dehydration, hydrogenation, and charge editing were performed using AutoDock software 4.2.6, resulting in the export of modified protein and compounds as PDBQT files. Docking was performed using AutoDock Vina software 1.2.0 [ 32 ]. Finally, the docking results were analyzed and visualized using Discovery Studio Visualizer v21.1.020298. 2.4 MD Simulation Molecular dynamics (MD) simulation using GROMACS 2022.6 ( https://manual.gromacs.org/2022-current/index.html ) [ 33 ] was employed to model the dynamic process of protein-ligand interactions which aided in validating the precision of drug design and supported the rationale of present study. The protein topology files were generated using the OPLS force field (Optimized Potential for Liquid Simulations, version 15) with the 'pdb2gmx' command. Ligand files for GROMACS were prepared using the external LigParagen web server ( https://traken.chem.yale.edu/ligpargen/ ) [ 34 , 35 , 36 ]. The protein was solvated in a dodecahedron box using a three-point water model, and neutralized with sodium (Na+) and chloride (Cl-) ions as counterions. The protein-ligand system was then subjected to energy minimization using the 'gmx grompp' and 'gmx mdrun' commands. Equilibration was carried out under NVT (Canonical) and NPT (Isobaric) ensembles, with the V-rescale thermostat applied to maintain a constant volume and temperature of 300 K. The complex was subjected to MD simulation run for 100 ns. To assess the stability of the complex, various analyses were conducted using the 'gmx rms' command, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) and hydrogen bond count (HBond). 3. Result and Discussion 3.1 Network Pharmacology 3.1.1 Target Prediction and Collection of T2DM Targets From the literature, 16 active constituents of karela (Momordicilin, Momordicoside C, Momorcharaside B, Momordin I, Cucurbitacin, Cycloartanol, Momordicoside A, Momordicoside L, Momordenol, Karounidiol, Momordicoside K, Momordicoside B, Momordicin, Cucurbitane, Charine, and Cucurbitine) were shortlisted and their SMILES and 3D structures downloaded from the PubChem database (Table:1). Using BindingDB and SwissTargetPrediction, 776 potential targets of the 16 active constituents of Karela were identified. For the collection of T2DM targets, the Open Target (5119 targets), TTD (187 targets), and DisGeNet (2826 targets) databases were used. The UniProt ID for each target was provided, and from the three databases, a final set of 104 T2DM targets was selected for study. A Venn diagram revealed 49 overlapping targets of T2DM and Karela, as listed in Table:2 , for further study. 3.1.2 Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment To explore the multiple functions of 49 targets, GO and KEGG analysis were performed. In GO analysis 279 biological process (BP), 34 cellular components (CC), and 46 molecular functions (MF) were enriched out of which top 10 BP, CC and MF have been represented in Fig. 1 A. The targets of karela in treating T2DM were primarily enriched in the following categories (i) Biological Processes (BP): positive regulation of gene expression, protein phosphorylation, inflammatory response, and signal transduction (ii) Cellular Components (CC): plasma membrane, cytoplasm, cytosol, and integral components of the membrane and (iii) Molecular Functions (MF): protein binding, ATP binding, integral protein binding, and protein serine/threonine/tyrosine kinase activity. The 140 pathways were enriched in KEGG analysis where the top 2 were found to be type 2 diabetes mellitus and Insulin resistance. The top 10 enriched pathways are depicted in Fig. 1 B. 3.1.3 Network Analysis The intersection targets of T2DM and Karela are presented as Venn diagram in Fig. 2 A. The PPI network of these 49 targets were generated using STRING database and analysed in cystoscope as depicted in Fig. 2 B. This network comprised of 49 nodes and 44 edges with an average node degree of 1.8 and a low PPI enrichment P-value of 4.83e-13. The MCODE plugin in Cytoscape was utilized to identify clusters representing highly interconnected areas within a network. In present study, this analysis unveiled a highly interconnected region and PRKCD as hub gene as depicted in Fig. 2 C. The Cytohubba plug in was used to identify top 10 genes from network, based on closeness and degree calculations, as shown in Fig. 2 D and Fig. 2 E. CytoNCA, which provides various centrality metrics for both, weighted and unweighted networks, was employed to analyse the selected network for closeness, betweenness, and degree calculations without applying weights. The identified top 10 highly interconnected genes are presented in Table: 3. Various studies have indicated that the overexpression of PRKCD leads to insulin resistance. Olivier B. et al. revealed in their study that in hepatic cells, the overexpression of PRKCD in C57BL/6J and 129S6/Sv mice resulted in glucose intolerance, insulin resistance and overexpression of gluconeogenic enzymes. PRKCD also plays a role in diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy [ 37 , 38 , 39 ]. Based on these studies, it can be concluded that PRKCD plays a significant role in the pathology of T2DM, and this target has been selected for further molecular docking and MD simulation studies. 3.1.4 Differential Gene Expression Analysis To prove further pathophysiological role of PRKCD in T2DM, we performed the gene expression analysis. The GSE26168 dataset ( https://www.ncbi.nlm.nih.gov/geoprofiles/74421147 ) was downloaded from GEO database. This study includes 24 patients (8 control, 7 with impaired fasting glucose and 9 with T2DM) and PRKCD levels in their blood were analysed. As shown in Fig. 3 , prediabetic patients with impaired fasting glucose exhibited significant overexpression of PRKCD in their blood compared to the control group and a similar overexpression of PRKCD was observed in T2DM patients. This indicates that identified gene PRKCD plays a crucial role in T2DM and inhibition of its expression may be an effective approach for treating T2DM. 3.2 Prediction of Binding Pocket Predicted binding pockets of PRKCD protein through CastP and PocketDepth servers shown in Table:4 . Amino acid involved in molecular docking interaction highlighted with yellow colour. 3.3 Molecular Docking Molecular docking of the 16 active constituents of Karela with the PRKCD protein was performed, and the molecular docking scores along with interactions with various amino acids are shown in Table:5 . The molecular docking score ranges from − 8.2 kcal/mol to -4.7 kcal/mol. The top scored compound, Momordicilin, did not shown any H-bonding with any amino acid. The top three compounds were Momordicoside C, Momorcharaside B and Momordin I with molecular docking score of -8.0 kcal/mol, -7.9 kcal/mol and − 7.9 kcal/mol respectively. Momordicoside C aglycone part formed H-bond with Ala23, Gln25, Arg75 with distance of 2.30 Å, 1.99 Å, 2.79 Å and 2.53 Å respectively. While Momorcharaside B aglycone group formed two H-bond with Pro26, Gln25 with distance of 2.46 Å and 2.30 Å respectively. Momordin I aglycone group formed H-bond with Ser5 with a distance of 2.26 Å and glycone part formed H-bond with Ile6, Gln8 (2 H-bond), Val11 (2 H-bond), Tyr52 and Thr58 with distance of 2.57 Å, 2.30 Å, 1.85 Å, 2.25 Å, 2.19 Å, 2.43 Å and 3.16 Å. The 2D and 3D interaction of top 3 compounds Momorcharaside B, Momordicoside C and Momordin I are presented in a Fig. 4 A, Fig. 4 B and Fig. 4 C. 3.4 MD Simulation The complex of PRKCD and ligand subjected to 100ns of MD simulation and the various parameters were measures like RMSD, RMSF, Rg and SASA. The RMSD is used for checking the stability of complex and lower RMSD value indicates the stable complex [ 40 – 43 ]. The RMSD of Momorcharaside B in Fig. 5 A. After 20 ns of fluctuation, the complex of PRKCD and Momorcharaside B (grey) became stable, with an RMSD value of around 1 nm, indicating a stable complex. The RMSD value of the PRKCD protein(blue) alone was also lower, around 0.2 nm. RMSF analysis describes the fluctuations of amino acids throughout the 100 ns simulation. A higher RMSF value signifies greater amino acid movement during the simulation [ 37 – 40 ]. The Fig. 5 B represents the RMSF of complex and its showed that there is less fluctuations and at the end of the simulation the RMSF value is around 0.7nm. For analysis of stability and folding properties of protein SASA was calculated [ 37 – 40 ]. The Fig. 5 C represents the SASA of protein(blue), Lig (orange) and complex (grey). The SASA value of protein and complex is almost same and there is no instability during the 100ns of simulation. The Rg value indicates the compactness and stability of system. The Fig. 5 D despites the Rg of Protein (blue), Lig (orange) and Complex(gray). After 20ns of fluctuations complex remain stable throughout the 100ns of simulation and after 70ns the protein and complex are overlapped and Rg value being less than 1.7nm and this indicates the stable system. Hydrogen bonding analysis is essential for characterizing ligand-protein interactions, as hydrogen bonds can influence the binding strength of small molecules [ 37 – 40 ]. As represented in Fig. 5 E PRKCD and Momorcharaside B complex formed the 3 H-bond at the end of the simulation. Figure 5 F represents the distance of donor- acceptor H-bond during the simulation. Figure 6 presents the MD simulation data for Momordicoside C. Figure 6 A showed the RMSD values of the system. Due to initial conformational changes in the protein during the first 25 ns, the RMSD value of the complex (grey) rose to 2 nm, but it stabilized, and by the end of the simulation, the RMSD value was close to 1 nm, indicating a stable and compact system. The RMSF value was observed to be around 1.4 nm (Fig. 6 B), and the SASA (Fig. 6 C) for both the complex (grey) and protein (blue) remained stable throughout the simulation. The Rg value of the complex (Fig. 6 D) fluctuated during the simulation. Up until 50 ns, the complex remained stable, but at 50 ns, there was a fluctuation with the Rg value reaching up to 4 nm. It stabilized again, but another fluctuation occurred at 70 ns. By the end of the 100 ns simulation, the Rg value was near 2 nm. Figure 6 E represents the number of hydrogen bonds formed during the simulation. From this MD analysis, It can conclude that the complex of Momordicoside C is quite stable. Figure 7 A showed the RMSD of Momordin I. As depicted, the complex remained stable between 20 to 70 ns, but fluctuations began afterward, with the RMSD rising to 3.5 nm. However, there was minimal fluctuation in the RMSF (Fig. 7 B) and SASA (Fig. 7 C), with the RMSF remaining close to 0.8 nm. The Rg of the complex (Fig. 7 D) was near 3.5 nm at the end of the simulation, although there was some instability throughout the process. By the end of the simulation, no hydrogen bond interactions were observed (Fig. 7 E), suggesting that the Momordin I complex is not stable. Figure 8 showed the amino acid interactions of all three compounds at 0 ns (Fig. 8 A), 50 ns (Fig. 8 B), and 100 ns (Fig. 8 C). By the end of the simulation, Momorcharaside B formed three hydrogen bonds, Momordicoside C formed four hydrogen bonds, and Momordin I did not form any hydrogen bonds with the PRKCD protein. Therefore, Momorcharaside B and Momordicoside C could act as potential PRKCD inhibitors for the treatment of T2DM. 4. Summary Type 2 diabetes mellitus being the most prevalent disorder, linked to insulin resistance and insufficient insulin production. Natural products, including Momordica charantia (bitter melon or karela), are increasingly explored for their anti-diabetic properties due to fewer side effects and affordability. Bitter melon contains several bioactive compounds like saponins and alkaloids, known for their hypoglycemic activity. This study aimed to explore additional anti-diabetic mechanisms of karela through network pharmacology, molecular docking, and MD simulation. Network pharmacology identified 49 overlapping targets between T2DM and karela, highlighting PRKCD as a key target. Gene expression analysis confirmed the overexpression of PRKCD in prediabetic and diabetic patients. PRKCD belongs to the family of serine/threonine protein kinases [ 44 ], and this was further confirmed by the GO enrichment study, where it was identified as a molecular function (Fig. 1 A). Figure 1 C illustrates the KEGG enrichment of PRKCD, and as shown in the figure, hyperglycemia triggers the activation of PRKCD, leading to insulin resistance. The PRKCD is also involved in various cellular process for developing T2DM [ 45 ]. Activation of this protein can increase the glucose level, this hyperglycemia condition can trigger the glycolysis pathway and increased synthesis of diacylglycerol (DAG) which ultimately leads activation protein kinase and this promotes the oxidative stress in body and as consequence of this it leads to cell death and apoptosis. [ 46 , 47 ]. So, deactivation of PRKCD can be beneficial for the tratemnet of T2DM. Molecular docking of 16 karela compounds with PRKCD revealed top-binding compounds: Momordicoside C, Momorcharaside B, and Momordin I. MD simulations demonstrated stable interactions between PRKCD and Momorcharaside B, suggesting potential as a PRKCD inhibitor, which could be beneficial for T2DM management. Figure 9 represents the proposed mechanism of Momorcharaside B, Momordicoside C in the treatment of T2DM. Deactivation of PRKCD can lead regulation of MAPK pathway and less/no generation of reactive oxygen species and no insulin resistance. 5. Conclusion In conclusion, this study highlights the therapeutic potential of Momordica charantia (bitter melon) as a natural remedy for T2DM. Through network pharmacology analysis, 49 target proteins were identified that link the active constituents of Momordica charantia to T2DM. Among these targets, PRKCD emerged as a key hub gene and it is associated with insulin resistance and diabetic complications. Molecular docking studies revealed that the active compounds Momorcharaside B, Momordicoside C, and Momordin I interact with PRKCD. Momorcharaside B and Momordicoside C demonstrating the most stable interactions during 100ns of molecular dynamics simulations. These findings suggest that these two compounds have the potential to act as PRKCD inhibitors, offering a novel mechanism for managing T2DM. The results provide a foundation for further research and development of Momordica charantia-derived treatments, emphasizing the role of natural products in combating chronic metabolic diseases like diabetes. Declarations Conflict of Interest Statement: Declared None CRediT Statement: Yadav Ruchi: Data Curation, Writing - Original Draft, Visualization; Nidhi Nambir and Manushi Shah : Collection of the data from various sources and databases; Patel Bhumika: Conceptualization, Methodology, Supervision, Writing - Review & Editing, English editing Acknowledgment : Authors are thankful to Nirma University, Ahmedabad, Gujarat, India for providing necessary facilities to carry out this research work. References Ogurtsova, K., da Rocha Fernandes, J. D., Huang, Y., Linnenkamp, U., Guariguata, L., Cho, N. H., ... & Makaroff, L. E. (2017). 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Possible overlap between 49 targets of T2DM and Karela Sr. No Uniprot ID Gene Name Sr. No Uniprot ID Gene Name 1 O00763 ACACB 26 MAPK1 P28482 2 P30542 ADORA1 27 MAPK3 P27361 3 P29275 ADORA2B 28 MAPK8 P45983 4 P13945 ADRB3 29 MAPK9 P45984 5 P29466 CASP1 30 METAP2 P50579 6 Q14790 CASP8 31 MGAM O43451 7 P32239 CCKBR 32 MTOR P42345 8 P32246 CCR1 33 NOD2 Q9HC29 9 P51681 CCR5 34 NR3C1 P04150 10 P00746 CFD 35 P2RX7 Q99572 11 P21554 CNR1 36 PIK3CA P42336 12 O75907 DGAT1 37 PIK3CB P42338 13 P00734 F2 38 PIK3CD O00329 14 P11362 FGFR1 39 PIK3CG P48736 15 P47871 GCGR 40 PPARA Q07869 16 Q8TDU6 GPBAR1 41 PPARD Q03181 17 Q8TDV5 GPR119 42 PRKCD Q05655 18 P49841 GSK3B 43 PRKCE Q02156 19 P52789 HK2 44 REN P00797 20 P28845 HSD11B1 45 SCD O00767 21 P80365 HSD11B2 46 SIRT1 Q96EB6 22 P28223 HTR2A 47 SLC10A2 Q12908 23 O14920 IKBKB 48 TLR9 Q9NR96 24 P01584 IL1B 49 TNF P01375 25 P06213 INSR Table 3. Top 10 highly interconnected genes based on closeness, betweenness, and degree using CytoNCA Sr. No Closeness Betweenness Degree Gene Name Score Gene Name Score Gene Name Score 1 PRKCD 0.12676056 PRKCD 256.0 PRKCD 8.0 2 MAPK3 0.123853214 MAPK3 196.0 PIK3CB 7.0 3 PIK3CB 0.12328767 TNF 190.0 PIK3CD 7.0 4 PIK3CD 0.12328767 MTOR 76.0 PIK3CA 7.0 5 PIK3CA 0.12328767 PIK3CB 56.333332 TNF 5.0 6 MAPK1 0.12 PIK3CD 56.333332 MTOR 4.0 7 TNF 0.119469024 PIK3CA 56.333332 PRKCE 4.0 8 PRKCE 0.11790393 SIRT1 40.0 INSR 4.0 9 MAPK9 0.1173913 IL1B 37.0 IL1B 4.0 10 MAPK8 0.1173913 CASP1 37.0 1CASP1 4.0 Table: 4 Predicated Binding Pockets of PRKCD CastP Server PocketDepth Server Sr. No Chain Residue No AminoAcid Sr. No Chain Residue No AminoAcid Sr. No Chain Residue No AminoAcid 1 A -2 Gly 40 A 63 Ile 1 A 14 Leu 2 A 0 His 41 A 64 Tyr 2 A 16 Ser 3 A 1 Met 42 A 65 Glu 3 A 17 Leu 4 A 2 Ala 43 A 66 Gly 4 A 18 Gln 5 A 3 Pro 44 A 67 Arg 5 A 19 Ala 6 A 4 Phe 45 A 69 Ile 6 A 22 Glu 7 A 5 Leu 46 A 74 Met 7 A 23 Ala 8 A 6 Arg 47 A 75 Arg 8 A 24 Asn 9 A 7 Ile 48 A 89 Ser 9 A 25 Gln 10 A 8 Ala 49 A 77 Ala 10 A 26 Pro 11 A 9 Phe 50 A 88 Val 11 A 27 Phe 12 A 14 Leu 51 A 89 Ser 12 A 28 Cys 13 A 18 Gln 52 A 91 Leu 13 A 50 Thr 14 A 24 Asn 53 A 94 Arg 14 A 51 Met 15 A 26 Pro 54 A 95 Cys 15 A 52 Tyr 16 A 27 Phe 55 A 96 Lys 16 A 53 Pro 17 A 28 Cys 56 A 99 Asn 17 A 54 Glu 18 A 30 Val 57 A 100 Gly 18 A 55 Trp 19 A 32 Met 58 A 101 Lys 19 A 57 Ser 20 A 33 Lys 59 A 102 Ala 20 A 58 Thr 21 A 34 Glu 60 A 104 Phe 21 A 59 Phe 22 A 40 Arg 61 A 117 Ser 22 A 60 Asp 23 A 41 Gly 62 A 118 Val 23 A 75 Arg 24 A 43 Thr 63 A 119 Gln 24 A 76 Ala 25 A 47 Lys 64 A 120 Tyr 25 A 77 Ala 26 A 48 Lys 65 A 121 Phe 26 A 79 Glu 27 A 49 Pro 66 A 122 Leu 27 B 8 Gln 28 A 50 Thr 67 A 123 Glu 28 B 10 Tyr 29 A 51 Met 68 B 2 Ala 29 B 11 Val 30 A 52 Tyr 69 B 3 Leu 30 B 12 Phe 31 A 53 Pro 70 B 4 Tyr 31 B 13 Ala 32 A 54 Glu 71 B 6 Ile 33 A 55 Trp 72 B 8 Gln 34 A 57 Ser 73 B 9 Pro 35 A 58 Thr 74 B 10 Tyr 36 A 59 Phe 75 B 11 Val 37 A 60 Asp 76 B 12 Phe 38 A 61 Ala 77 B 13 Ala 39 A 62 His Table 5. Molecular docking interaction of active constituents of Karela Sr. no Compound Name Molecular Docking Score (kcal/mol) Amino acid interaction (H-bond) Amino acid interaction (Hydrophobic) 1 Momordicilin -8.2 NA Tyr10, Phe12, Phe27, Tyr52 2 Momordicoside C -8.0 Glycone: Tyr10 Aglycone: Ala23, Gln25, Arg75 Glycone: Tyr52, Aglycone: Phe27, Ala76 3 Momorcharaside B -7.9 Aglycone: PRO26, GLN25 Glycone: Ala13, Ala23, Phe27, Tyr52 4 Momordin I -7.9 Aglycone: Ser5, Ile6 Glycone: Gln8, Val11, Tyr52, Thr58 Glycone: Thr58 5 Cucurbitacin -7.7 NA Ala13, Tyr52 6 Cycloartanol -7.6 NA Tyr10, Phe12, Ala13, Phe27, Tyr52 7 Momordicoside A -7.4 Glycone: Tyr10, Val11 Aglycone: Gln25, Glu54 Aglycone: Phe27, Trp55, Ala77 8 Momordicoside L -7.4 Aglycone: Phe27, Tyr52, Trp55 Glycone: Tyr52 9 Momordenol -7.2 NA Phe27, Tyr52, Ala77, Met74 10 Karounidiol -7.1 NA Ala13, Phe27, Tyr52 11 Momordicoside K -7.1 Glycone: Tyr10, Val11 Aglycone: Phe27, Trp55 12 Momordicoside B -7.1 Glycone: Ala23, Gln25, Pro53 Aglycone: Tyr10, Val11, Ala13, Tyr52 13 Momordicin -7.0 NA Ala23, Gln25, Phe27 14 Cucurbitane -6.9 NA Ala13, Phe27, Tyr52 15 Charine -5.7 Asp60, His62, Arg67 Lys48 16 Cucurbitine -4.7 NA Gln8, Asp60, His62 Additional Declarations No competing interests reported. Supplementary Files Table1.docx Cite Share Download PDF Status: Published Journal Publication published 07 Jul, 2025 Read the published version in In Silico Pharmacology → Version 1 posted Editorial decision: Revision requested 10 Mar, 2025 Reviews received at journal 20 Feb, 2025 Reviewers agreed at journal 15 Feb, 2025 Reviews received at journal 13 Feb, 2025 Reviewers agreed at journal 13 Feb, 2025 Reviewers agreed at journal 13 Feb, 2025 Reviewers agreed at journal 13 Feb, 2025 Reviewers invited by journal 13 Feb, 2025 Editor assigned by journal 03 Feb, 2025 Submission checks completed at journal 03 Feb, 2025 First submitted to journal 03 Feb, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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The size of the bars is arranged in the descending order of the number of genes \u003cstrong\u003eB) \u003c/strong\u003eKEGG pathway analysis of the top 10 targets. The bar color is displayed in a gradient from red to blue in ascending order of the p-value \u003cstrong\u003eC)\u003c/strong\u003e KEGG Enrichment of PRKCD\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/029daa6143eec29fdb4ce586.png"},{"id":75520267,"identity":"4750d8f1-eed3-418e-9581-49975e1295c9","added_by":"auto","created_at":"2025-02-05 12:02:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3205411,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA)\u003c/strong\u003e Venn diagram of targets of karela and T2DM \u003cstrong\u003eB)\u003c/strong\u003e Network of 49 targets \u003cstrong\u003eC)\u003c/strong\u003e Cluster 1 analysed by MCODE \u003cstrong\u003eD)\u003c/strong\u003e Top 10 genes based on closeness. Shades of red from dark to light indicates the genes from top to bottom in the list \u003cstrong\u003eE)\u003c/strong\u003e Top 10 genes based on degree. Shades of color: dark red indicates 1 number gene\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/a6b786e6584a4c880a94f4e4.png"},{"id":75520261,"identity":"16f7af96-de7d-47fd-9e80-9af90d4302e4","added_by":"auto","created_at":"2025-02-05 12:02:11","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":935937,"visible":true,"origin":"","legend":"\u003cp\u003eGene expression of PRKCD in patient study\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/97aa9919f5fbc1a85e7b0be2.png"},{"id":75519711,"identity":"d173af18-34be-43df-94be-1b44aa074aab","added_by":"auto","created_at":"2025-02-05 11:54:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3792101,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular docking result \u003cstrong\u003eA)\u003c/strong\u003e 2D and 3D amino acid interaction of Momorcharaside B \u003cstrong\u003eB)\u003c/strong\u003e 2D and 3D amino acid interaction of Momordicoside C \u003cstrong\u003eC)\u003c/strong\u003e 2D and 3D amino acid interaction of Momordin I\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/62c9181234d591c3bddbfefe.png"},{"id":75521245,"identity":"cd9ff9aa-1346-4169-ae90-6f59ea729e5e","added_by":"auto","created_at":"2025-02-05 12:10:12","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1733818,"visible":true,"origin":"","legend":"\u003cp\u003ePRKCD interactions with the Momorcharaside B monitored during the 100 ns of simulation \u003cstrong\u003eA)\u003c/strong\u003eRMSD value (Protein: Blue, Momorcharaside B: Orange, Complex: Grey), \u003cstrong\u003eB)\u003c/strong\u003e RMSF of Complex \u003cstrong\u003eC)\u003c/strong\u003e SASA value (Protein: Blue, Momorcharaside B: Orange, Complex:Grey) \u003cstrong\u003eD)\u003c/strong\u003e Rg (Protein: Blue, Momorcharaside B: Orange, Complex: Grey) \u003cstrong\u003eE)\u003c/strong\u003e Number of H-bond \u003cstrong\u003eF)\u003c/strong\u003e Hydrogen bond distribution\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/d40fee5528221e0024812c24.png"},{"id":75520249,"identity":"c721e9ef-ddec-403b-adbc-6933687fbffd","added_by":"auto","created_at":"2025-02-05 12:02:09","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1736538,"visible":true,"origin":"","legend":"\u003cp\u003ePRKCD interactions with the Momordicoside C monitored during the 100 ns of simulation \u003cstrong\u003eA)\u003c/strong\u003e RMSD value (Protein: Blue, Momordicoside C: Orange, Complex: Grey), \u003cstrong\u003eB)\u003c/strong\u003e RMSF of Complex \u003cstrong\u003eC)\u003c/strong\u003e SASA value (Protein: Blue, Momordicoside C: Orange, Complex: Grey) \u003cstrong\u003eD)\u003c/strong\u003e Rg (Protein: Blue, Momordicoside C: Orange, Complex: Grey) \u003cstrong\u003eE)\u003c/strong\u003e Number of H-bond \u003cstrong\u003eF)\u003c/strong\u003e Hydrogen bond distribution\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/086a42e1516a4704be09cfdc.png"},{"id":75519720,"identity":"b50745ba-7e13-4df4-8d92-8f83e267aa04","added_by":"auto","created_at":"2025-02-05 11:54:13","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1504199,"visible":true,"origin":"","legend":"\u003cp\u003ePRKCD interactions with the Momordin I, monitored during the 100 ns of simulation \u003cstrong\u003eA)\u003c/strong\u003e RMSD value (Protein: Blue, Momordin I: Orang, Complex: Grey), \u003cstrong\u003eB)\u003c/strong\u003e RMSF of Complex \u003cstrong\u003eC)\u003c/strong\u003e SASA value (Protein: Blue, Momordin I: Orang, Complex: Grey) \u003cstrong\u003eD)\u003c/strong\u003e Rg (Protein: Blue, Momordin I: Orang, Complex: Grey) \u003cstrong\u003eE)\u003c/strong\u003e Number of H-bond \u003cstrong\u003eF)\u003c/strong\u003e Hydrogen bond distribution\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/cd4b2f982c5f659d8fcc3216.png"},{"id":75521554,"identity":"c5782ecc-d596-439f-a6cd-5b844d71a0c7","added_by":"auto","created_at":"2025-02-05 12:18:10","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":2833902,"visible":true,"origin":"","legend":"\u003cp\u003e2D Amino acid interaction during of Momorcharaside B, Momordicoside C and Momordin I during MD Simulation \u003cstrong\u003eA)\u003c/strong\u003eInteraction at 0ns \u003cstrong\u003eB)\u003c/strong\u003e Interaction at 50ns \u003cstrong\u003eC)\u003c/strong\u003e Interaction at 100ns\u003c/p\u003e","description":"","filename":"Figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/37bfd997ff01e0e40ca1f8b5.png"},{"id":75520250,"identity":"85393f14-84cd-448d-8fba-4be9136ca5f7","added_by":"auto","created_at":"2025-02-05 12:02:10","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":1908324,"visible":true,"origin":"","legend":"\u003cp\u003eProposed mechanism action of Momorcharaside B and Momordicoside C targeting PRKCD\u003c/p\u003e","description":"","filename":"Figure9.png","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/3fa09c9484af71e15a99adfb.png"},{"id":86699327,"identity":"1aa01964-d6c3-4bbf-845c-71e6094f8cc3","added_by":"auto","created_at":"2025-07-14 16:07:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":19992569,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/42606f4b-cbae-488a-8d1c-b30013ba71c0.pdf"},{"id":75521243,"identity":"d1f5ba97-c6e2-43dc-a83d-54a2f979a220","added_by":"auto","created_at":"2025-02-05 12:10:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":247766,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5948998/v1/6063d894b1e8d66376a93985.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exploring the Therapeutic Potential of Momordica charantia in Targeting Protein Kinase C Delta (PRKCD) for Type 2 Diabetes Mellitus: Insights from Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations ","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eDiabetes mellitus is a serious metabolic disease that affects human health. There are three types of diabetes: type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. T2DM is a chronic condition caused by decreased insulin production and increased insulin resistance and is prevalent worldwide, with a 49% increase since 1990. In 2019, there were 437.9\u0026nbsp;million reported cases of T2DM, primarily in low- and middle-income countries [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. T2DM is associated with metabolic diseases such as obesity and increases the risk of heart disease, which is the leading cause of death globally[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Currently, mainstream treatments for T2DM include pharmacological agents and lifestyle modification, but these are limited by side effects and cost [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Natural products, such as herbal remedies, have become an increasingly popular alternative treatment for T2DM as they have fewer side effects and low cost. The use of natural substances for the treatment of diabetes is considered a promising strategy that may provide solutions for the limitations of current treatments [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePlants and their products play a crucial role in nutrition by providing essential nutrients and aiding in the prevention of various illnesses, ultimately enhancing the quality of life worldwide. Traditional plant-based medicines have been used for centuries, but it is important to standardize them to evaluate their potential benefits [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The Momordica charantia is widely popular plant in India. Commonly it is known as \u0026ldquo;bitter melon\u0026rdquo; and in Hindi as \u0026ldquo;karela\u0026rdquo;. This plant belongs to family Cucurbitaceae [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Traditionally, bitter melon has been known for its potent antidiabetic, anticancer, anti-inflammatory, antiviral and cholesterol-lowering medicinal properties [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The plant contains several biologically active compounds, including glycosides, saponins, alkaloids, triterpenes, proteins, and steroids. The hypoglycemic activity of Momordica charantia is primarily attributed to its saponins, collectively known as charantins, and alkaloids. These saponins have been shown to lower blood glucose levels in both animal studies and clinical trials. Additionally, several phytochemicals isolated from the plant, such as charantins, polypeptide-p, momordin Ic, oleanolic acid 3-O-monodesmoside, and oleanolic acid 3-O-glucuronide, have been found to exhibit hypoglycemic activity. These compounds enhance insulin secretion, increase glucose uptake, and reduce glucose production in the liver. Overall, the presence of various bioactive compounds in Momordica charantia makes it a promising natural remedy for diabetes management [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, due to the presence of multiple compounds and multiple targets in Karela, its underlying mechanism has not been thoroughly explored. In present study we explored the anti-diabetic mechanism of this plant by using a network pharmacology study and validated through molecular docking and molecular dynamic (MD) simulation study. The network pharmacology study is emerging computational technique for drug discovery and development. Initially, the bioactive compounds of Karela were screened, and the overlapping targets between Karela and T2DM were identified. Protein-protein interaction (PPI) networks and core targets were then established through network topological structure analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to determine the functions and pathways associated with the overlapping targets. Lastly, molecular docking and molecular dynamic (MD) simulations were performed to evaluate the compound-target binding affinity based on the network pharmacology results. The study outcome aids the identification of novel possible targets of plant constituents and enrichment pathways against T2DM.\u003c/p\u003e"},{"header":"2. Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Network Pharmacology\u003c/h2\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003e2.1.1 Compound mining and target predictions of active constituents of karela\u003c/h2\u003e \u003cp\u003eActive compounds from Momordica charantia L. were chosen by conducting a literature survey, and their SMILES were subsequently downloaded using PubChem (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubchem.ncbi.nlm.nih.gov/\u003c/span\u003e\u003cspan address=\"https://pubchem.ncbi.nlm.nih.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). BindingDB [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.bindingdb.org/rwd/bind/index.jsp\u003c/span\u003e\u003cspan address=\"https://www.bindingdb.org/rwd/bind/index.jsp\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and SwissTargetPrediction (STP) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.swisstargetprediction.ch/\u003c/span\u003e\u003cspan address=\"https://www.swisstargetprediction.ch/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) were explored against these active compounds to predict their respective target genes focusing on a \"\u003cem\u003ehomo sapiens\u003c/em\u003e\" keyword.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.1.2 Collection of T2DM targets\u003c/h2\u003e \u003cp\u003eT2DM related targets were searched using keywords\u0026rsquo; \u0026ldquo;diabetes\u0026rdquo;, \u0026ldquo;diabetes mellitus\u0026rdquo;, type 2 diabetes mellitus\u0026rdquo;, \u0026ldquo;insulin-independent diabetes\u0026rdquo;, \u0026ldquo;diabetes mellitus type 2\u0026rdquo; in databases such as DisGeNET (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://disgenet.com/\u003c/span\u003e\u003cspan address=\"https://disgenet.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], Therapeutic Target Database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://db.idrblab.net/ttd/\u003c/span\u003e\u003cspan address=\"https://db.idrblab.net/ttd/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and Open Target (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.opentargets.org/\u003c/span\u003e\u003cspan address=\"https://www.opentargets.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The target names were matched to their corresponding UniProt IDs (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.uniprot.org/\u003c/span\u003e\u003cspan address=\"https://www.uniprot.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Venny 2.1 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://bioinfogp.cnb.csic.es/tools/venny/\u003c/span\u003e\u003cspan address=\"https://bioinfogp.cnb.csic.es/tools/venny/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] was utilized to identify overlapping targets from all three databases. The common targets of T2DM, retrieved from three databases, and the identified targets of active compounds of Karela, obtained from SwissTargetPrediction and BindingDB databases, were uploaded into Venny 2.1 to create a Venn diagram showing the overlap between T2DM targets and the targets of Karela's active constituents. The intersection of targets from this Venn diagram was then used for further studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.1.3 PPI Network of Intersected Gene\u003c/h2\u003e \u003cp\u003eTo further investigate the mechanism of action of active constituents of karela in the treatment of T2DM, the intersection of 49 targets was imported into String. Protein-protein interactions were analysed using String ver. 11.0 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://string‐db.org/\u003c/span\u003e\u003cspan address=\"https://string‐db.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The minimum combined score was set to 0.9 and protein-protein‐interaction (PPI) relationships for \u0026ldquo;\u003cem\u003eHomo sapiens\u0026rdquo;\u003c/em\u003e were obtained. Targets without interaction were removed and the data were saved as SIF files. Next, the PPI network was constructed by importing node1 and node2 into Cytoscape [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Finally, the core targets were screened by cluster analysis using the MCODE [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], CytoHubba [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and CytoNCA [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] plugin of Cytoscape.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.1.4 GO and KEGG Enrichment Analysis\u003c/h2\u003e \u003cp\u003eThe GO enrichment analysis was conducted through the utilization of the DAVID (Database for Annotation, Visualization and Integrated Discovery) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://david.ncifcrf.gov/tools.jsp\u003c/span\u003e\u003cspan address=\"https://david.ncifcrf.gov/tools.jsp\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) database [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The Biological Process (BP), Cellular Component (CC), and Molecular Function (MF) modules were chosen and significant biological annotations (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were selected for analysis. Additionally, KEGG pathway [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] enrichment analysis was conducted to identify the principal signaling pathways involved in T2DM using the DAVID database and the graph for KEGG and GO plotted by using SRPLOT(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://bioinformatics.com.cn/en\u003c/span\u003e\u003cspan address=\"https://bioinformatics.com.cn/en\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.1.5 Different Gene Expression Analysis\u003c/h2\u003e \u003cp\u003eThrough network analysis of 49 predicted targets, Protein Kinase C Delta Type (PRKCD) was identified as a hub gene. To determine whether this target is involved in the pathophysiology of T2DM, gene expression analysis was performed using the GEO database. In this database, term \u0026ldquo;PRKCD\u0026rdquo; was searched along with \u0026ldquo;\u003cem\u003eHomo sapiens\u0026rdquo;\u003c/em\u003e as filer under species tab. The GSE26168 dataset (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE26168\u0026amp;platform=GPL6883\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE26168\u0026amp;platform=GPL6883\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was selected, and GEO2R analysis was performed to download the data. This study involved 24 participants, including 8 controls, 7 with impaired fasting glucose, and 9 with T2DM. PRKCD levels in the blood were analyzed in these groups.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Prediction of Binding Pocket\u003c/h2\u003e \u003cp\u003eIn this study, PRKCD was identified as a hub gene through network analysis. However, it does not have a native ligand in the PDB. Therefore, prior to molecular docking, the binding pockets were identified using the CastpFold server (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cfold.bme.uic.edu/castpfold/\u003c/span\u003e\u003cspan address=\"https://cfold.bme.uic.edu/castpfold/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), which provides detailed information on the topological and geometrical features, as well as pocket details, of the uploaded protein [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Additionally, the PocketDepth server (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://proline.physics.iisc.ernet.in/pocketdepth/\u003c/span\u003e\u003cspan address=\"http://proline.physics.iisc.ernet.in/pocketdepth/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), a computational tool for identifying binding pockets in protein structures, was utilized [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Molecular Docking\u003c/h2\u003e \u003cp\u003eMolecular docking is a computational method used to study the interactions between a protein and a ligand [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Initially, all compounds of Karela were searched for in the PubChem database, and the structures were exported in 3D \u0026lsquo;mol2\u0026rsquo; format. Subsequently, the 3D structure of the core protein Protein Kinase C Delta Type (PRKCD) (PDB ID: 1YRK, 1.7\u0026Aring;) was downloaded from the Protein Data Bank (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.rcsb.org/\u003c/span\u003e\u003cspan address=\"https://www.rcsb.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The processes of dehydration, hydrogenation, and charge editing were performed using AutoDock software 4.2.6, resulting in the export of modified protein and compounds as PDBQT files. Docking was performed using AutoDock Vina software 1.2.0 [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Finally, the docking results were analyzed and visualized using Discovery Studio Visualizer v21.1.020298.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.4 MD Simulation\u003c/h2\u003e \u003cp\u003eMolecular dynamics (MD) simulation using GROMACS 2022.6 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://manual.gromacs.org/2022-current/index.html\u003c/span\u003e\u003cspan address=\"https://manual.gromacs.org/2022-current/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] was employed to model the dynamic process of protein-ligand interactions which aided in validating the precision of drug design and supported the rationale of present study. The protein topology files were generated using the OPLS force field (Optimized Potential for Liquid Simulations, version 15) with the 'pdb2gmx' command. Ligand files for GROMACS were prepared using the external LigParagen web server (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://traken.chem.yale.edu/ligpargen/\u003c/span\u003e\u003cspan address=\"https://traken.chem.yale.edu/ligpargen/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The protein was solvated in a dodecahedron box using a three-point water model, and neutralized with sodium (Na+) and chloride (Cl-) ions as counterions. The protein-ligand system was then subjected to energy minimization using the 'gmx grompp' and 'gmx mdrun' commands. Equilibration was carried out under NVT (Canonical) and NPT (Isobaric) ensembles, with the V-rescale thermostat applied to maintain a constant volume and temperature of 300 K. The complex was subjected to MD simulation run for 100 ns. To assess the stability of the complex, various analyses were conducted using the 'gmx rms' command, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) and hydrogen bond count (HBond).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Result and Discussion","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Network Pharmacology\u003c/h2\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e3.1.1 Target Prediction and Collection of T2DM Targets\u003c/h2\u003e \u003cp\u003eFrom the literature, 16 active constituents of karela (Momordicilin, Momordicoside C, Momorcharaside B, Momordin I, Cucurbitacin, Cycloartanol, Momordicoside A, Momordicoside L, Momordenol, Karounidiol, Momordicoside K, Momordicoside B, Momordicin, Cucurbitane, Charine, and Cucurbitine) were shortlisted and their SMILES and 3D structures downloaded from the PubChem database \u003cb\u003e(Table:1).\u003c/b\u003e Using BindingDB and SwissTargetPrediction, 776 potential targets of the 16 active constituents of Karela were identified. For the collection of T2DM targets, the Open Target (5119 targets), TTD (187 targets), and DisGeNet (2826 targets) databases were used. The UniProt ID for each target was provided, and from the three databases, a final set of 104 T2DM targets was selected for study. A Venn diagram revealed 49 overlapping targets of T2DM and Karela, as listed in \u003cb\u003eTable:2\u003c/b\u003e, for further study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e3.1.2 Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment\u003c/h2\u003e \u003cp\u003eTo explore the multiple functions of 49 targets, GO and KEGG analysis were performed. In GO analysis 279 biological process (BP), 34 cellular components (CC), and 46 molecular functions (MF) were enriched out of which top 10 BP, CC and MF have been represented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA. The targets of karela in treating T2DM were primarily enriched in the following categories (i) Biological Processes (BP): positive regulation of gene expression, protein phosphorylation, inflammatory response, and signal transduction (ii) Cellular Components (CC): plasma membrane, cytoplasm, cytosol, and integral components of the membrane and (iii) Molecular Functions (MF): protein binding, ATP binding, integral protein binding, and protein serine/threonine/tyrosine kinase activity. The 140 pathways were enriched in KEGG analysis where the top 2 were found to be type 2 diabetes mellitus and Insulin resistance. The top 10 enriched pathways are depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.1.3 Network Analysis\u003c/h2\u003e \u003cp\u003eThe intersection targets of T2DM and Karela are presented as Venn diagram in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA. The PPI network of these 49 targets were generated using STRING database and analysed in cystoscope as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB. This network comprised of 49 nodes and 44 edges with an average node degree of 1.8 and a low PPI enrichment P-value of 4.83e-13. The MCODE plugin in Cytoscape was utilized to identify clusters representing highly interconnected areas within a network. In present study, this analysis unveiled a highly interconnected region and PRKCD as hub gene as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC. The Cytohubba plug in was used to identify top 10 genes from network, based on closeness and degree calculations, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE. CytoNCA, which provides various centrality metrics for both, weighted and unweighted networks, was employed to analyse the selected network for closeness, betweenness, and degree calculations without applying weights. The identified top 10 highly interconnected genes are presented in \u003cb\u003eTable: 3.\u003c/b\u003e Various studies have indicated that the overexpression of PRKCD leads to insulin resistance. Olivier B. et al. revealed in their study that in hepatic cells, the overexpression of PRKCD in C57BL/6J and 129S6/Sv mice resulted in glucose intolerance, insulin resistance and overexpression of gluconeogenic enzymes. PRKCD also plays a role in diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Based on these studies, it can be concluded that PRKCD plays a significant role in the pathology of T2DM, and this target has been selected for further molecular docking and MD simulation studies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e3.1.4 Differential Gene Expression Analysis\u003c/h2\u003e \u003cp\u003eTo prove further pathophysiological role of PRKCD in T2DM, we performed the gene expression analysis. The GSE26168 dataset (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/geoprofiles/74421147\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/geoprofiles/74421147\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was downloaded from GEO database. This study includes 24 patients (8 control, 7 with impaired fasting glucose and 9 with T2DM) and PRKCD levels in their blood were analysed. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, prediabetic patients with impaired fasting glucose exhibited significant overexpression of PRKCD in their blood compared to the control group and a similar overexpression of PRKCD was observed in T2DM patients. This indicates that identified gene PRKCD plays a crucial role in T2DM and inhibition of its expression may be an effective approach for treating T2DM.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Prediction of Binding Pocket\u003c/h2\u003e \u003cp\u003ePredicted binding pockets of PRKCD protein through CastP and PocketDepth servers shown in \u003cb\u003eTable:4\u003c/b\u003e. Amino acid involved in molecular docking interaction highlighted with yellow colour.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Molecular Docking\u003c/h2\u003e \u003cp\u003eMolecular docking of the 16 active constituents of Karela with the PRKCD protein was performed, and the molecular docking scores along with interactions with various amino acids are shown in \u003cb\u003eTable:5\u003c/b\u003e. The molecular docking score ranges from \u0026minus;\u0026thinsp;8.2 kcal/mol to -4.7 kcal/mol. The top scored compound, Momordicilin, did not shown any H-bonding with any amino acid. The top three compounds were Momordicoside C, Momorcharaside B and Momordin I with molecular docking score of -8.0 kcal/mol, -7.9 kcal/mol and \u0026minus;\u0026thinsp;7.9 kcal/mol respectively. Momordicoside C aglycone part formed H-bond with Ala23, Gln25, Arg75 with distance of 2.30 \u0026Aring;, 1.99 \u0026Aring;, 2.79 \u0026Aring; and 2.53 \u0026Aring; respectively. While Momorcharaside B aglycone group formed two H-bond with Pro26, Gln25 with distance of 2.46 \u0026Aring; and 2.30 \u0026Aring; respectively. Momordin I aglycone group formed H-bond with Ser5 with a distance of 2.26 \u0026Aring; and glycone part formed H-bond with Ile6, Gln8 (2 H-bond), Val11 (2 H-bond), Tyr52 and Thr58 with distance of 2.57 \u0026Aring;, 2.30 \u0026Aring;, 1.85 \u0026Aring;, 2.25 \u0026Aring;, 2.19 \u0026Aring;, 2.43 \u0026Aring; and 3.16 \u0026Aring;. The 2D and 3D interaction of top 3 compounds Momorcharaside B, Momordicoside C and Momordin I are presented in a Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e3.4 MD Simulation\u003c/h2\u003e \u003cp\u003eThe complex of PRKCD and ligand subjected to 100ns of MD simulation and the various parameters were measures like RMSD, RMSF, Rg and SASA. The RMSD is used for checking the stability of complex and lower RMSD value indicates the stable complex [\u003cspan additionalcitationids=\"CR41 CR42\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The RMSD of Momorcharaside B in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA. After 20 ns of fluctuation, the complex of PRKCD and Momorcharaside B (grey) became stable, with an RMSD value of around 1 nm, indicating a stable complex. The RMSD value of the PRKCD protein(blue) alone was also lower, around 0.2 nm. RMSF analysis describes the fluctuations of amino acids throughout the 100 ns simulation. A higher RMSF value signifies greater amino acid movement during the simulation [\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB represents the RMSF of complex and its showed that there is less fluctuations and at the end of the simulation the RMSF value is around 0.7nm. For analysis of stability and folding properties of protein SASA was calculated [\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC represents the SASA of protein(blue), Lig (orange) and complex (grey). The SASA value of protein and complex is almost same and there is no instability during the 100ns of simulation. The Rg value indicates the compactness and stability of system. The Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD despites the Rg of Protein (blue), Lig (orange) and Complex(gray). After 20ns of fluctuations complex remain stable throughout the 100ns of simulation and after 70ns the protein and complex are overlapped and Rg value being less than 1.7nm and this indicates the stable system. Hydrogen bonding analysis is essential for characterizing ligand-protein interactions, as hydrogen bonds can influence the binding strength of small molecules [\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. As represented in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE PRKCD and Momorcharaside B complex formed the 3 H-bond at the end of the simulation. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eF represents the distance of donor- acceptor H-bond during the simulation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e presents the MD simulation data for Momordicoside C. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA showed the RMSD values of the system. Due to initial conformational changes in the protein during the first 25 ns, the RMSD value of the complex (grey) rose to 2 nm, but it stabilized, and by the end of the simulation, the RMSD value was close to 1 nm, indicating a stable and compact system. The RMSF value was observed to be around 1.4 nm (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB), and the SASA (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eC) for both the complex (grey) and protein (blue) remained stable throughout the simulation. The Rg value of the complex (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eD) fluctuated during the simulation. Up until 50 ns, the complex remained stable, but at 50 ns, there was a fluctuation with the Rg value reaching up to 4 nm. It stabilized again, but another fluctuation occurred at 70 ns. By the end of the 100 ns simulation, the Rg value was near 2 nm. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eE represents the number of hydrogen bonds formed during the simulation. From this MD analysis, It can conclude that the complex of Momordicoside C is quite stable.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eA showed the RMSD of Momordin I. As depicted, the complex remained stable between 20 to 70 ns, but fluctuations began afterward, with the RMSD rising to 3.5 nm. However, there was minimal fluctuation in the RMSF (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eB) and SASA (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eC), with the RMSF remaining close to 0.8 nm. The Rg of the complex (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eD) was near 3.5 nm at the end of the simulation, although there was some instability throughout the process. By the end of the simulation, no hydrogen bond interactions were observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003eE), suggesting that the Momordin I complex is not stable. Figure\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e showed the amino acid interactions of all three compounds at 0 ns (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003eA), 50 ns (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003eB), and 100 ns (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003eC). By the end of the simulation, Momorcharaside B formed three hydrogen bonds, Momordicoside C formed four hydrogen bonds, and Momordin I did not form any hydrogen bonds with the PRKCD protein. Therefore, Momorcharaside B and Momordicoside C could act as potential PRKCD inhibitors for the treatment of T2DM.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Summary","content":"\u003cp\u003eType 2 diabetes mellitus being the most prevalent disorder, linked to insulin resistance and insufficient insulin production. Natural products, including Momordica charantia (bitter melon or karela), are increasingly explored for their anti-diabetic properties due to fewer side effects and affordability. Bitter melon contains several bioactive compounds like saponins and alkaloids, known for their hypoglycemic activity. This study aimed to explore additional anti-diabetic mechanisms of karela through network pharmacology, molecular docking, and MD simulation.\u003c/p\u003e \u003cp\u003eNetwork pharmacology identified 49 overlapping targets between T2DM and karela, highlighting PRKCD as a key target. Gene expression analysis confirmed the overexpression of PRKCD in prediabetic and diabetic patients. PRKCD belongs to the family of serine/threonine protein kinases [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], and this was further confirmed by the GO enrichment study, where it was identified as a molecular function (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC illustrates the KEGG enrichment of PRKCD, and as shown in the figure, hyperglycemia triggers the activation of PRKCD, leading to insulin resistance. The PRKCD is also involved in various cellular process for developing T2DM [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Activation of this protein can increase the glucose level, this hyperglycemia condition can trigger the glycolysis pathway and increased synthesis of diacylglycerol (DAG) which ultimately leads activation protein kinase and this promotes the oxidative stress in body and as consequence of this it leads to cell death and apoptosis. [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. So, deactivation of PRKCD can be beneficial for the tratemnet of T2DM. Molecular docking of 16 karela compounds with PRKCD revealed top-binding compounds: Momordicoside C, Momorcharaside B, and Momordin I. MD simulations demonstrated stable interactions between PRKCD and Momorcharaside B, suggesting potential as a PRKCD inhibitor, which could be beneficial for T2DM management. Figure\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e represents the proposed mechanism of Momorcharaside B, Momordicoside C in the treatment of T2DM. Deactivation of PRKCD can lead regulation of MAPK pathway and less/no generation of reactive oxygen species and no insulin resistance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, this study highlights the therapeutic potential of Momordica charantia (bitter melon) as a natural remedy for T2DM. Through network pharmacology analysis, 49 target proteins were identified that link the active constituents of Momordica charantia to T2DM. Among these targets, PRKCD emerged as a key hub gene and it is associated with insulin resistance and diabetic complications. Molecular docking studies revealed that the active compounds Momorcharaside B, Momordicoside C, and Momordin I interact with PRKCD. Momorcharaside B and Momordicoside C demonstrating the most stable interactions during 100ns of molecular dynamics simulations. These findings suggest that these two compounds have the potential to act as PRKCD inhibitors, offering a novel mechanism for managing T2DM. The results provide a foundation for further research and development of Momordica charantia-derived treatments, emphasizing the role of natural products in combating chronic metabolic diseases like diabetes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement:\u003c/strong\u003e Declared None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT Statement:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYadav Ruchi:\u0026nbsp;\u003c/strong\u003eData Curation, Writing - Original Draft, Visualization; \u003cstrong\u003eNidhi Nambir\u003c/strong\u003e and \u003cstrong\u003eManushi Shah\u003c/strong\u003e: Collection of the data from various sources and databases; \u003cstrong\u003ePatel Bhumika:\u003c/strong\u003e Conceptualization, Methodology, Supervision, Writing - Review \u0026amp; Editing, English editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e: Authors are thankful to Nirma University, Ahmedabad, Gujarat, India for providing necessary facilities to carry out this research work.\u0026nbsp;\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOgurtsova, K., da Rocha Fernandes, J. 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Trends Pharmacol Sci (2006) 27(6):317\u0026ndash;23. doi: 10.1016/j.tips.2006.04.003\u003c/li\u003e\n\u003cli\u003eJang JH, Kim EA, Park HJ, Sung EG, Song IH, Kim JY, et al. Methylglyoxal-induced apoptosis is dependent on the suppression of c-FLIP(L) expression via down-regulation of p65 in endothelial cells. J Cell Mol Med (2017) 21(11):2720\u0026ndash;31. doi: 10.1111/jcmm.13188\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Possible overlap between 49 targets of T2DM and Karela\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUniprot\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGene Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUniprot\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGene Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eO00763\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eACACB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMAPK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP28482\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP30542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eADORA1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMAPK3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP27361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP29275\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eADORA2B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMAPK8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP45983\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP13945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eADRB3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMAPK9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP45984\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP29466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCASP1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMETAP2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP50579\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eQ14790\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCASP8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMGAM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eO43451\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP32239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCCKBR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e32\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMTOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP42345\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP32246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCCR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e33\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eNOD2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ9HC29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP51681\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCCR5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e34\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eNR3C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP04150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP00746\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eP2RX7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ99572\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP21554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCNR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e36\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP42336\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eO75907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eDGAT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e37\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP42338\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP00734\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eF2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e38\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eO00329\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP11362\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eFGFR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e39\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP48736\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP47871\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGCGR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e40\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePPARA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ07869\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eQ8TDU6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGPBAR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e41\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePPARD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ03181\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e17\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eQ8TDV5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGPR119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePRKCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ05655\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP49841\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGSK3B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e43\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePRKCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ02156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP52789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eHK2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eREN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eP00797\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP28845\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eHSD11B1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eSCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eO00767\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP80365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eHSD11B2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e46\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eSIRT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ96EB6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP28223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eHTR2A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e47\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eSLC10A2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ12908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eO14920\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eIKBKB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eTLR9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eQ9NR96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP01584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eIL1B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e49\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eTNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eP01375\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP06213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eINSR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Top 10 highly interconnected genes based on closeness, betweenness, and degree using CytoNCA\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCloseness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBetweenness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDegree\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGene Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eScore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGene Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eScore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGene Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eScore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003ePRKCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.12676056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePRKCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e256.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003ePRKCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003eMAPK3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.123853214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMAPK3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e196.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003ePIK3CB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003ePIK3CB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.12328767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eTNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e190.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003ePIK3CD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003ePIK3CD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.12328767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eMTOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e76.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003ePIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003ePIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.12328767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e56.333332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eTNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003eMAPK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e56.333332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMTOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003eTNF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.119469024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003ePIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e56.333332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003ePRKCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003ePRKCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.11790393\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eSIRT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e40.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eINSR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003eMAPK9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.1173913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eIL1B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e37.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eIL1B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003eMAPK8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.1173913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003eCASP1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e37.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1CASP1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable: 4 Predicated Binding Pockets of PRKCD\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCastP Server\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePocketDepth Server\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidue No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAminoAcid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidue No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAminoAcid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResidue No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAminoAcid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eIle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eHis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eSer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eMet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGln\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eArg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eIle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eMet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eArg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eArg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAsn\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eIle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eSer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGln\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eVal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eSer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eCys\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGln\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eThr\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAsn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eArg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eMet\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eCys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e17\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eCys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAsn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eVal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTrp\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eMet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eSer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eThr\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eArg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eSer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAsp\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eVal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eArg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eThr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGln\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGln\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eThr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eMet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eVal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eLeu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e32\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGlu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eIle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e33\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTrp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eGln\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e34\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eSer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eThr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eTyr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e36\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eVal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e37\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAsp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ePhe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e38\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e39\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eHis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 5. Molecular docking interaction of active constituents of Karela\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"708\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr. no\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCompound Name\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMolecular Docking Score (kcal/mol)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAmino acid interaction\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(H-bond)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAmino acid interaction (Hydrophobic)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicilin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-8.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eTyr10, Phe12, Phe27, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicoside C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eGlycone: Tyr10 Aglycone: Ala23, Gln25, Arg75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eGlycone: Tyr52, Aglycone: Phe27, Ala76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomorcharaside B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eAglycone: PRO26, GLN25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eGlycone: Ala13, Ala23, Phe27, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordin I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eAglycone: Ser5, Ile6 Glycone: Gln8, Val11, Tyr52, Thr58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eGlycone: Thr58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCucurbitacin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAla13, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCycloartanol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eTyr10, Phe12, Ala13, Phe27, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicoside A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eGlycone: Tyr10, Val11 Aglycone: Gln25, Glu54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAglycone: Phe27, Trp55, Ala77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicoside L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eAglycone: Phe27, Tyr52, Trp55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eGlycone: Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordenol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003ePhe27, Tyr52, Ala77, Met74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eKarounidiol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAla13, Phe27, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicoside K\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eGlycone: Tyr10, Val11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAglycone: Phe27, Trp55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicoside B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eGlycone: Ala23, Gln25, Pro53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAglycone: Tyr10, Val11, Ala13, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMomordicin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAla23, Gln25, Phe27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCucurbitane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eAla13, Phe27, Tyr52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCharine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eAsp60, His62, Arg67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eLys48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCucurbitine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003eGln8, Asp60, His62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"in-silico-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"insp","sideBox":"Learn more about [In Silico Pharmacology](https://link.springer.com/journal/40203)","snPcode":"40203","submissionUrl":"https://submission.nature.com/new-submission/40203/3","title":"In Silico Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"T2DM, PRKCD, Karela, Momordicoside C, Momorcharaside B, Network Pharmacology, Molecular Docking, MD Simulation","lastPublishedDoi":"10.21203/rs.3.rs-5948998/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5948998/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eType 2 diabetes mellitus (T2DM) is a chronic condition caused by decreased insulin production and increased insulin resistance, and its prevalence has increased by 49% since 1990. Current treatments for T2DM include pharmacological agents and lifestyle modifications, but they are limited by their side effects and cost. Herbal remedies and natural products have become popular alternative treatments for T2DM as they are associated with fewer side effects. Momordica charantia Linn. (bitter melon) is a member of the Cucurbitaceae family and has been used as a traditional anti-diabetic remedy in various countries for many years. The plant contains several biologically active compounds, including glycosides, saponins, alkaloids, triterpenes, proteins, and steroids. The hypoglycemic activity of Momordica charantia is primarily attributed to its saponins, which are collectively known as charantins, and alkaloids.\u003c/p\u003e \u003cp\u003eThrough network pharmacology, Molecular docking and MD simulation we found underlying, mechanism of karela in the treatment of T2DM. Through network pharmacology from 49 targets we found the Protein kinase C delta (PRKCD) as a hub gene. Various studies have also indicated the pathophysiological role of PRKCD in the development of T2DM. Gene expression analysis in 24 patients revealed an overexpression of PRKCD in both prediabetic and diabetic patients. Molecular docking data identified the top three active constituents of karela as Momordicoside C, Momorcharaside B, and Momordin I, with docking scores of -8.0 kcal/mol, -7.9 kcal/mol, and \u0026minus;\u0026thinsp;7.9 kcal/mol, respectively. Additionally,MD simulation was performed using the GROMACS software and we found that Momordicoside C and Momorcharaside B has good stability and also formed the H-bond at end of the 100ns of simulation. This study revelled new mechanism action of a well-known plant karela in the treatment of T2DM.\u003c/p\u003e","manuscriptTitle":"Exploring the Therapeutic Potential of Momordica charantia in Targeting Protein Kinase C Delta (PRKCD) for Type 2 Diabetes Mellitus: Insights from Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-05 11:53:52","doi":"10.21203/rs.3.rs-5948998/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-10T18:43:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-20T11:20:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12008648302010659045895862338503521688","date":"2025-02-15T14:17:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-13T18:34:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329314384695751169650458952726465926272","date":"2025-02-13T16:37:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"296219807731877483277446134052291813259","date":"2025-02-13T14:41:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157783828108919654575036411189598200001","date":"2025-02-13T14:16:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-02-13T14:01:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-03T14:07:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-02-03T14:04:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"In Silico Pharmacology","date":"2025-02-03T06:59:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"in-silico-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"insp","sideBox":"Learn more about [In Silico Pharmacology](https://link.springer.com/journal/40203)","snPcode":"40203","submissionUrl":"https://submission.nature.com/new-submission/40203/3","title":"In Silico Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"33357c2b-a622-4301-95c7-25a6400321a6","owner":[],"postedDate":"February 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T16:00:08+00:00","versionOfRecord":{"articleIdentity":"rs-5948998","link":"https://doi.org/10.1007/s40203-025-00385-7","journal":{"identity":"in-silico-pharmacology","isVorOnly":false,"title":"In Silico Pharmacology"},"publishedOn":"2025-07-07 15:57:09","publishedOnDateReadable":"July 7th, 2025"},"versionCreatedAt":"2025-02-05 11:53:52","video":"","vorDoi":"10.1007/s40203-025-00385-7","vorDoiUrl":"https://doi.org/10.1007/s40203-025-00385-7","workflowStages":[]},"version":"v1","identity":"rs-5948998","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5948998","identity":"rs-5948998","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}