In silico bioprospecting of receptors for Oligoventin: an antimicrobial peptide isolated from spider eggs of Phoneutria nigriventer

In silico bioprospecting of receptors for Oligoventin: an antimicrobial peptide isolated from spider eggs of Phoneutria nigriventer | 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 In silico bioprospecting of receptors for Oligoventin: an antimicrobial peptide isolated from spider eggs of Phoneutria nigriventer Elias Jorge Muniz Seif, Pedro Ismael da Silva Junior This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4013832/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Irresponsible and wholesale use of antimicrobial agents is the principal cause of the emergence of strains of resistant microorganisms to traditional drugs. Oligoventin is a neutral peptide isolated from spider eggs of Phoneutria nigriventer , with antimicrobial activity against Gram-positive, Gram-negative, and yeast organisms. However, the molecular target and pathways of antimicrobial activity are still unknown. Thus, the aim of the present study is to prospect receptors associated with the antimicrobial activity of Oligoventin using in silico tools. Methods The PharmMapper server was used to prospect targets originating from microorganisms. Additionally, the PatchDock server was utilized to perform molecular docking between Oligoventin and the targets. Subsequently, the I-TASSER server was adopted to predict the ligand site. Finally, the docking results and predicted sites were compared with literature sites of each target. Results Twenty-two potential receptors for Oligoventin were identified. Among these, Enoyl-ACP reductase (Id pdb 1lxc) and Thymidylate synthase ThyX (Id pdb 1O28) demonstrated superior interaction with the peptide, exhibiting co-localization between docked residues and literature sites. These enzymes play a crucial role in fatty acid and DNA biosynthesis in prokaryotes Conclusion Therefore, in silico results suggest that Oligoventin can impair fatty acid and DNA synthesis, thereby reducing microbial proliferation and causing microorganism death. Bioinformatics Applied Biochemistry Computational Biology Molecular Docking Simulation Protein Domains DNA Metabolism Enzymes Figures Figure 1 Figure 2 Introduction Bacteria are unicellular organisms with an unstructured nucleus, known as prokaryotes. They are closely associated with human activities. In general, this association is beneficial to humanity ( 1 ). However, it can also be a disharmonious relationship, with parasitism being the main cause of disease ( 2 – 4 ). Thus, microorganisms are also associated with impairments in agriculture, the food industry, and public health as: Salmonella typhi ( 5 ), Streptococcus pyogenes ( 6 ) and Mycobacterium tuberculosis ( 7 ). The emergence of microorganisms resistant to traditional drugs is increasing each year, primarily due to the irresponsible and widespread use of antimicrobial agents, coupled with the high mutational capacity of certain bacterial strains. Studies indicate that multidrug-resistant organisms may lead to the deaths of 10 million people per year by 2050, making it the leading cause of mortality in humans and resulting in an estimated expenditure of over $ 100 trillion on public health systems worldwide ( 8 , 9 ). The development of new antimicrobial drugs is crucial in mitigating the impact caused by resistant organisms. Peptides or peptidic-derived biomolecules, which are amino acid polymers, offer an alternative to combating resistant organisms. Once these molecules are associated with antimicrobial activity, they exhibit a high capacity for analog production ( 10 , 11 ). Oligoventin (COOH-QPFSLERW-NH 2 ) is a neutral and amphiphilic peptide isolated from spider eggs of Phoneutria nigriventer . This molecule exhibits antimicrobial activity against Gram-positive bacteria ( Micococcus luteus, Staphylococcus aureus , and Staphylococcus epidermidis ) with minimal inhibitory concentrations (MIC) ranging from 47.2 to 188.9 µM ( 12 ). Additionally, it demonstrates activity against Gram-negative strains ( Serratia marcescens ) with MIC ranging from 25.7 to 47.2 µM ( 12 , 13 ). Furthermore, it displays antifungal activity against Candida albicans and Candida auris , with MIC lower than 1 mM. However, the molecular target and mechanism of action of this peptide remain unknown. Computational tools are currently utilized for simulating biological and physicochemical phenomena. These tools are commonly used in protein chemistry, enabling the evaluation of molecular three-dimensional structure, folding, interactions, docking, and dynamics ( 14 – 17 ). In silico methods offer the principal advantage of reducing the time and cost associated with screening assays. Therefore, the aim of this study was to prospect receptors associated with the antimicrobial activity of the Oligoventin peptide using bioinformatics tools ( in silico ). Methods Peptide Characterization and Folding To determine the physicochemical parameters of the peptide (net charge, hydrophobicity, hydrophobic moment, and molecular weight), the amino acid sequence of Oligoventin (COOH-QPFSLERW-NH 2 ) was submitted to the Heliquest server ( 18 ). The three-dimensional structure and free energy minimization were performed using UCSF Chimera software ( 19 ) with the following settings: 1000 steps of steepest descent, steepest descent step size of 0.02 Å, 10 steps of conjugate gradient, conjugate gradient step size of 0.02 Å, update interval of 10, and no fixed atoms after hydrogen addition, hydrogen bond addition, charges, and side-chain torsion (using the amber force field ff14SB). Targets Prospection The PharmMapper server was utilized to identify potential receptors for Oligoventin ( 20 ). The Oligoventin structure was submitted to the server with the following parameters: Generate Conformers (YES), Maximum Generated Conformations (300), and full/complete pharmacophore mapping with all Targets selected (v2010, 7302), and a number of Reserved Matched Targets (300). The top 50 best-ranked targets based on normalized fit score were chosen, and further filtered by microbial origin (Gram-positive or Gram-negative). Consequently, 22 targets were selected for this study, and the structure of each target was downloaded from the Protein Data Bank (PDB) server. Molecular Docking The PatchDock server was employed to conduct molecular docking between Oligoventin (ligand) and all 22 targets identified in PharmMapper (receptors) ( 21 ). PatchDock server parameters were set to Clustering RMSD (4.0) and Complex Type (Default). For each receptor, the best solution (conformation) was determined by collecting Score, Area, ACE (effective atomic contact energies), and transformation value. Ultimately, the highest score value was used to assess the optimal binding of Oligoventin. Ligand and Receptor interaction The software UCSF Chimera was utilized to analyze the interaction between Oligoventin and the receptors ( 22 ). The FindHBond tool was configured with relaxed constraints (2 Å and 20 degrees) to identify hydrogen bonds. Only hydrogen atoms with a distance of less than 4 Å between their heavy atoms were considered in this study. Additionally, information regarding electron donor/acceptor and residue interactions between the ligand and receptor was collected. Ligand binding site prediction The I-TASSER (protein function & function prediction) server was employed to identify binding sites for receptors ( 23 ). In this study, only the top 6 receptors (based on major docking scores) were selected for analysis. For polymeric proteins, only one chain was used for this analysis. Subsequently, the predicted binding sites were compared with those found by docking analysis to assess the accuracy of receptor selection. Results Peptide characterization Oligoventin (COOH-QPFSLERW-NH2) is a neutral peptide with a net charge of 0, comprising 8 amino acids with a molecular weight of 1062.18 g/mol and an isoelectric point of pH 6.58. This peptide consists of half hydrophilic and half hydrophobic residues, with two of them being aromatic, resulting in an extinction coefficient of 5690 M − 1 cm − 1 , indicating good water solubility. Additionally, in silico energy minimization of the peptide structure yielded − 852.55 kJ/mol. This molecule was utilized to perform simulations in this study. Targets Prospection After performing the initial search on the PharmMapper server, 300 potential receptors were identified (Table S1). These were filtered by their origin from microorganisms (Gram-positive or Gram-negative), resulting in 22 targets with normalized fit scores ranging from 0.9912 to 0.9313 (Table 1 ). The top three receptors based on their score are Urocanate hydratase (1W1U), Aspartate aminotransferase (1TOI), and Copper-containing nitrite reductase (1RZP), ranked as 3, 4, and 9, respectively, in the general rank. Conversely, the receptors with the lowest fit scores are A/G-specific adenine glycosylase (1WEI), 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (1U3L), and DNA protection during starvation protein 2 (1JI5), ranked as 50, 47, and 42, respectively, in the general rank (Table 1 ). Table 1 PharmMapper search results using Oligoventin as a ligand PM Rank PDB ID Target Name Normalized Fit Score Origin Gram 3 1W1U Urocanate hydratase 0.9912 Pseudomonas putida - 4 1TOI Aspartate aminotransferase 0.9903 Escherichia coli - 9 1RZP Copper-containing nitrite reductase 0.9817 Achromobacter cycloclastes - 10 1SFJ 3-dehydroquinate dehydratase 0.9811 Staphylococcus aureus subsp. aureus MRSA252 + 14 1UDX Hypothetical protein 0.9732 Thermus thermophilus HB8 - 15 1KSS Fumarate reductase flavoprotein subunit 0.9723 Shewanella frigidimarina - 16 1O28 Thymidylate synthase thyX 0.9698 Thermotoga maritima - 17 1LXC Enoyl-ACP Reductase 0.9697 Escherichia coli - 18 1M5W Pyridoxine 5-phosphate synthase 0.9673 Escherichia coli - 22 1B6G Haloalkane dehalogenase 0.9617 Xanthobacter autotrophicus - 24 1UFY Chorismate mutase 0.9582 Thermus thermophilus HB8 - 27 1UXG Malate dehydrogenase 0.9554 Chloroflexus aurantiacus - 33 1VMA Cell division protein FtsY 0.9463 Thermotoga maritima - 34 1Y54 Beta-lactamase 0.946 Enterobacter cloacae - 35 1BO5 Glycerol kinase 0.9446 Escherichia coli - 37 1VMK Purine nucleoside phosphorylase 0.9418 Thermotoga maritima MSB8 - 38 1UKQ Cyclomaltodextrin glucanotransferase 0.9404 Bacillus sp. 1011 + 39 1TDJ Threonine dehydratase biosynthetic 0.9403 Escherichia coli - 40 2PIL Fimbrial protein 0.9402 Neisseria gonorrhoeae - 42 1JI5 DNA protection during starvation protein 2 0.9386 Bacillus anthracis + 47 1U3L 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 0.9339 Escherichia coli - 50 1WEI A/G-specific adenine glycosylase 0.9313 Escherichia coli - PM Rank (General PharmMapper rank search), PDB ID (Identification code in protein data bank), Normalized Fit Score (value obtained by ratio of fit score and number of features), Origin (Specie form the target was isolated), + (Gram-positive), - (Gram-Negative). Molecular docking results Docking results showed a range of scores (10982 to 5308), areas (1493.9 to 679.9), and ACE values (289.21 to -290.26). The rankings obtained from the PatchDock server differed from those presented by PharmMapper. The complete results are provided in Table S2. In the molecular docking analysis, Thymidylate synthase ThyX (Id pdb 1O28), Pyridoxine 5-phosphate synthase (Id pdb 1M5W), Threonine dehydratase biosynthetic (Id pdb 1TDJ), Enoyl-ACP reductase (Id pdb 1LXC), Fumarate reductase flavoprotein subunit (1KSS), and Cyclomaltodextrin glucanotransferase (Id pdb 1UKQ) exhibited top dock scores. Additionally, these targets showed similar interaction areas, ranging from 1492.9 to 881.2. However, targets 1TDJ (-2.33), 1LXC (-290.26), and 1KSS (-218.38) presented negative values for ACE (Table 2 ). In contrast, targets with lower dock scores included Fimbrial protein (Id pdb 2PIL), Haloalkane dehalogenase (Id pdb 1B6G), Chorismate mutase (Id pdb 1UFY), and 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (Id pdb 1U3L). All of these targets exhibited interaction areas less than 800 and positive values of ACE (Table 2 ). Table 2 Docking results by PatchDock server. Oligoventin was used as ligand, and target obtained by PharmMapper was used as receptor. PM Rank PDB ID Receptor Name Score Area (Ų) ACE (Kcal/mol) 16 1O28 Thymidylate synthase thyX 10982 1493.9 289.21 18 1M5W Pyridoxine 5-phosphate synthase 8982 999.2 255.89 39 1TDJ Threonine dehydratase biosynthetic 8046 1072.1 -2.33 17 1LXC Enoyl-ACP reductase 7904 1105.1 -290.26 15 1KSS Fumarate reductase flavoprotein subunit 7776 1238.1 -218.38 38 1UKQ Cyclomaltodextrin glucanotransferase 7698 881.2 114.28 35 1BO5 Glycerol kinase 7640 1067 139.05 37 1VMK Purine nucleoside phosphorylase 7438 882.5 276.17 9 1RZP Copper-containing nitrite reductase 7286 837.6 5.66 27 1UXG Malate dehydrogenase 7258 921.8 -126.08 14 1UDX Hypothetical protein 7128 930.3 -195.07 4 1TOI Aspartate aminotransferase 6996 886.1 -136.05 34 1Y54 Beta-lactamase 6982 928.4 43.77 3 1W1U Urocanate hydratase 6824 1033.1 210.99 50 1WEI A/G-specific adenine glycosylase 6782 858.6 -24.09 33 1VMA Cell division protein FtsY 6614 792.9 184.82 42 1JI5 DNA protection during starvation protein 2 6398 798.2 248.52 10 1SFJ 3-dehydroquinate dehydratase 6374 765.8 -73.11 47 1U3L 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 6068 661.8 99.21 24 1UFY Chorismate mutase 5696 721.1 108.96 22 1B6G Haloalkane dehalogenase 5566 770.8 102.31 40 2PIL Fimbrial protein 5308 697.9 28.03 PM Rank (General PharmMapper rank search), PDB ID (Identification code in protein data bank), ACE (Atomic efective contact energy - Kcal/mol) Receptor and ligand binding analysis To simplify the analysis, only hydrogen bonds (≤ 4Å) were considered in the docking results, and the entire binding interactions are summarized in Table S3. In all interactions observed, Oligoventin acted as the electron donor, while the receptor served as the acceptor. No association was found between the number of hydrogen bonds and the dock score. Thymidylate synthase ThyX (4 bonds) exhibited interactions among HIS5.L -> Thr 101.RB , Gln1.L -> Glu 58RA / Thr 161.RB , and Arg 7.L -> Glu 54.RA . Pyridoxine 5-phosphate synthase and Threonine dehydratase biosynthetic showed 1 bond each, with receptor Gln 1.L -> Glu 240.RD and Gln 1.L -> Glu 324.R , respectively. Finally, Enoyl-ACP reductase (3 bonds) demonstrated interactions among Gln 1.L -> Gly 13.RB / Ser 19.RB and Arg 7.L -> ILE 192.RB (Table 3 ) Table 3 Hydrogens H-Bond (≤ 4Å) between receptor and Oligoventin obtained by a docking result of Patchdock Server PM Rank PDB ID Receptor Name Donor Acceptor D-A distance (Å) 16 1O28 Thymidylate synthase thyX HIS 5.L NE2 GLN 1.L NE2 GLN 1.L NE2 ARG 7.L NH2 THR 101.R B O GLU 58.R A O THR 161.R B O GLU 54.R A OE2 3.717 3.850 3.875 3.426 18 1M5W Pyridoxine 5-phosphate synthase GLN 1.L N GLU 240.R D OE2 2.394 39 1TDJ Threonine dehydratase biosynthetic GLN 1.L N GLU 324.R OE2 2.669 17 1LXC Enoyl-ACP Reductase GLN 1.L N GLN 1.L N ARG 7.L NE GLY 13.R B O SER 19.R B OG ILE 192.R B O 3.964 2.872 3.705 15 1KSS Fumarate reductase flavoprotein subunit N/B N/B N/B 38 1UKQ Cyclomaltodextrin glucanotransferase GLN 1.L NE2 GLN 1.L NE2 ARG 7.L NE ARG 7.L NH2 TYR 406.R B O GLY 502.R B O THR 409.R B O THR 409.R B O 3.764 2.401 3.795 3.574 35 1BO5 Glycerol kinase PHE 3.L N THR 14.R A OG1 3.528 37 1VMK Purine nucleoside phosphorylase GLN 1.L NE2 ARG 140.R C O 3.195 9 1RZP Copper-containing nitrite reductase N/B N/B N/B 27 1UXG Malate dehydrogenase GLN 1.L N GLY 79.R B O 3.810 14 1UDX Hypothetical protein ARG 7.L NH1 ALA 368.R O 3.872 4 1TOI Aspartate aminotransferase GLN 1.L N ARG 7.L NH2 THR 59.R O TYR 288.R O 2.486 3.441 34 1Y54 Beta-lactamase GLN 1.L N SER 4.L OG ARG 7.L NH2 SER 310.R OG SER 281.R OG ASP 280.R OD1 2.763 3.649 3.244 3 1W1U Urocanate hydratase SER 4.L OG ARG 7.L NH2 ASN 6.R A OD1 ASN 6.R A OD1 2.263 3.908 50 1WEI A/G-specific adenine glycosylase ARG 7.L NH2 GLN 33.R OE1 3.238 33 1VMA Cell division protein FtsY SER 4.L N ARG 7.L NH1 ARG 7.L NH2 GLN 1.L O ASN 80.R B O ASN 80.R B O 2.847 3.423 3.93 42 1JI5 DNA protection during starvation protein 2 GLN 1.L N PHE 36.RA O 3.504 10 1SFJ 3-dehydroquinate dehydratase ARG 7.L NH2 TYR 15.R B OH 2.327 47 1U3L 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase GLN 1.L N ARG 7.L NH2 ASP 55.R OD2 ASP 38.R OD1 3.453 3.435 24 1UFY Chorismate mutase N/B N/B N/B 22 1B6G Haloalkane dehalogenase ARG 7.L NH2 GLN 181.R O 3.858 40 2PIL Fimbrial protein GLN 1.L N ARG 7.L NE TRP 111.R O ASP 145.R OD1 1.641 3.806 Donor (Electron donor residue), Acceptor (Electron acceptor residue), D-A distance (distance between heavy atoms of electron acceptor and donor), GLY 1.L N (Residue name/ Number/ Chain ID/ Shared electron atom), L (Ligand ID), Rx (ReceptorSubunit ID) Receptor and ligand binding analysis Ligand binding site predictions were conducted for the six receptors with the highest dock scores. The major C-Scores are presented in Table 4 , while all ligand site predictions can be found in Table S4. Receptors 1O28 (Score = 0.42; Size = 45), 1M5W (Score = 0.93; Size = 141), 1TDJ (Score = 0.97; Size = 200), 1KSS (Score = 0.88; Size = 128), and 1UKQ (Score = 0.86; Size = 108) did not exhibit co-location between predicted and docked residues. Only receptor 1LXC (Score = 0.86; Size = 702) shared residues between both models. The co-localized residues were 13, 19, 91, 192, and 194 (Table 4 and Figs. 1 – 2 ). Table 4 Bind site co-location among predicted (I-TASSER), found in study (PatchDock) and literature descripted. Only one protein chain was used in this analysis. In bold residue shared for bind site models. PM Rank PDB ID Cluster Score Cluster size Ligand bind site residues (Prediction) Ligand bind site residues (Found) 16 1O28 0.42 45 42, 65, 67, 70, 93, 175, 177 39,40, 54ra,54ra, 163ra, 163rc, 165ra, 165rc, 169rc, 172rc 211ra, 211rc, 211rc 18 1M5W 0.93 141 72, 94, 133, 153, 192, 193, 194, 213, 214, 215, 216 228ra, 228ra, 235rf, 236rf, 236rg, 236rg, 240rd, 39 1TDJ 0.97 200 60, 61, 62, 87, 88, 89, 90, 157, 186, 188, 189, 190, 191, 192, 241, 242, 286, 288, 315, 316 320r, 320r, 321r, 323r, 324r, 458r, 461r 17 1LXC 0.86 704 13 , 15, 16, 19 , 20, 39, 40, 41, 63, 64, 65, 91 , 92, 93, 94, 119, 144, 145, 146, 159, 163, 189, 190, 191, 192 , 194 , 195, 196, 197 13rb , 19rb , 91rb ( 2 ), 97rb, 192rb , 194rb ( 3 ) 15 1KSS 0.88 128 132, 133, 134, 135, 136, 137, 156, 157, 158, 162, 163, 164, 165, 167, 168, 169, 170, 171, 276, 277, 278, 312, 313, 314, 336, 337, 338, 344, 375, 504, 505, 533, 534, 544, 547, 548, 549, 550, 553 44r, 52r, 53r( 2 ), 74r, 423r, 426r 38 1UKQ 0.68 108 100, 140, 194, 197, 227, 229, 230, 257, 327, 328 311rb( 2 ), 406rb( 2 ), 409rb( 2 ), 424rb, 502rb, 576rb, Cluster Score (confidence score of the prediction, ranges [0–1]), Cluster size (total number of templates in a cluster). Discussion The principal molecular pathways of antimicrobial molecules involve the impairment of protein, lipid, cell wall, genetic material synthesis, and membrane injury ( 24 ). Cationic amphiphilic peptides primarily exert their action mechanism through membrane interaction and disruption ( 25 , 26 ). This occurs due to their physicochemical properties; the positively charged peptide is attracted to the negatively charged bacterial plasma membrane ( 27 ). Subsequently, its amphiphilic characteristics enable the peptide to embed into the bacterial membrane, forming toroidal pores, barrel-stave pores, or carpet-like structures, leading to electrolytic imbalance and ultimately cell death ( 28 – 30 ). However, this mechanism is not specific, and cationic peptides are potentially cytotoxic ( 31 ). However, some peptides interact with intracellular targets, inhibiting protein (e.g., Pleurocidin, Apidaecin Hb1a), lipid (e.g., Mersacidin, MBI-28), and DNA (e.g., Buforin II, Ostricacin-1) biosynthesis, thereby harming microbial development ( 24 ). The Heliquest results showed that Oligoventin is a neutral and hydrophilic peptide. Furthermore, experimental assays demonstrated that this peptide does not exhibit cytotoxicity against fresh human blood cells at a concentration of 500µM ( 32 ). Both results suggest that the antimicrobial activity of Oligoventin is associated with intracellular pathways, interfering with bacterial homeostasis. PharmMapper is an online reverse docking tool that identifies targets using a mapping approach. After conducting the necessary methodology, 22 potential receptors for Oligoventin originating from both Gram-positive and Gram-negative microorganisms were identified. Subsequently, molecular docking was performed using PatchDock, revealing the best targets as thymidylate synthase ThyX (Id pdb 1O28), pyridoxine 5-phosphate synthase (Id pdb 1M5W), threonine dehydratase biosynthetic (Id pdb 1TDJ), enoyl-ACP reductase (Id pdb 1LXC), fumarate reductase flavoprotein subunit (Id pdb 1KSS), and cyclomaltodextrin glucanotransferase (Id pdb 1UKQ). Moreover, only receptors 1LXC and 1TDJ exhibited negative ACE values, suggesting thermodynamically favorable interactions between Oligoventin and these receptors ( 33 , 34 ). Notably, only enoyl-ACP reductase (Id pdb 1LXC) showed co-localization between the docked and ligand site predicted by I-TASSER (Fig. 1 – 2 ). Thymidylate synthase ThyX is an enzyme implicated in prokaryotic cell DNA synthesis, with two principal sites: the FAD + cofactor site (Asn 16 , Ser 30 , Thr 55 , His 79 , Glu 86 , and Arg 165 ) and the dUMP substrate site (Arg 78 , Glu 86 , Ser 88, Arg 90 , Arg 147 and Arg 174 ,) ( 34 – 36 ). The dock simulation revealed co-localization with Arg 165 , present in the FAD + cofactor site. However, no residues were co-localized with the predicted site from the I-TASSER server (Table 4 and Fig. 2 a – 2 b). Despite this, this receptor was discarded as a potential molecular target for Oligoventin due to the positive ACE value, indicating that the interaction is thermodynamically unfavorable in vitro assays. Pyridoxine 5-phosphate synthase is an enzyme associated with B6 vitamin synthesis, serving as an important cofactor in amino acid metabolism and glycogenolysis. This enzyme forms a complex with 1-deoxy-D-xylulose phosphate (dXP), involving residues such as Asp 11 , His 12 , Arg 20, His 52 , Glu 72 , Thr 103 , Glu 153 , and His 193 ( 37 , 38 ). While the dock simulation did not reveal shared residues with the dXP site, the predicted model exhibited co-localization with Glu 153 , Glu 72 and His 193 (Table 4 and Fig. 1 a). Threonine dehydratase biosynthetic is an important enzyme in the biosynthesis of the amino acid threonine in E. coli. This structure contains a Pyridoxal 5-phosphate (PLP) binding site composed of Phe 61 , Lys 62 , Asn 89 , Gly 241 and Ser 315 ( 39 , 40 ). Although the dock simulation did not reveal shared residues with PLP, all residues were shared with the predicted binding site (Table 4 and Fig. 1 b). Enoyl-ACP reductase is a key enzyme in the final step of type II fatty acid synthesis, specifically in the elongation phase. This molecule contains a cofactor binding site, with one binding site for NAD + comprising residues Ala 16 , Ala 41 , Leu 45 , Asp 67 , Val 68 , Ile 95 , and Ile 121 and another for the nicotinamide ring comprising Thr 147 , Tyr 148 , Ala 191 , Gly 192 , and Ile 194 ( 40 – 42 ). Both the dock simulation and predicted site revealed co-location with the residues Gly 192 and Ile 194 , which are present in the nicotinamide ring binding site (Table 4 and Fig. 2 c – 2 d). Fumarate reductase flavoprotein subunit is enzyme associated with bacteria respiration in oxygen absence, which are closely related to succinate dehydrogenase. This molecule has FAD + cofactor site (Glu 534 ) and subtracts (His 504 ) ( 43 , 44 ). Both residues not associated with Oligoventin in dock simulation results. In contrast, they are present in predicted binding site (Table 4 and Fig. 1 c). Cyclomaltodextrin glucanotransferase is enzyme associated to carbohydrates metabolism, important in cyclization of D-glucose. The substrate site is formed by Tyr 100 , Phe 183 , Tyr 195 , Asp 229 , Phe 259 and Asp 328 ( 45 ). Dock simulation not shows shared residues with substrate site, however Asp229 residues was shared with predicted bind site (Table 4 and Fig. 1 d). Therefore, molecular docking simulations suggest that Oligoventin interacts more strongly with Enoyl-ACP reductase (Id pdb 1LXC) and with less avidity with Thymidylate synthase ThyX (Id pdb 1O28), potentially disrupting the normal functions of these enzymes. This interaction could lead to a decrease in fatty acid and DNA biosynthesis, ultimately reducing microbial proliferation and impacting bacterial homeostasis. Conclusion The in silico bioprospecting of receptors for the antimicrobial activity of Oligoventin proved to be highly efficient, identifying only two targets from a database containing over seven thousand enzymes. The integration of software tools, including PharmMapper for target search, PatchDock for molecular docking, I-TASSER for ligand site prediction, and literature validation, was instrumental in validating each step of the analysis. In this study, Enoyl-ACP reductase and Thymidylate synthase ThyX emerged as the most promising targets, showing consistent results across docking, prediction, and literature binding sites. These enzymes are associated with fatty acid and DNA synthesis in prokaryotic organisms. Thus, Oligoventin's interaction with these targets may disrupt their normal function by competing for cofactor or substrate binding sites, ultimately reducing microbial proliferation and leading to bacterial death, consistent with previous antibacterial in vitro assays. This study paves the way for further research into the interaction between receptors and ligands using molecular dynamics ( in silico ) or enzymology assays ( in vitro ). Furthermore, it suggests the potential for designing new Oligoventin analogs to enhance antimicrobial efficacy and explore other biological potentials, such as antitumoral and anti-inflammatory properties. Declarations Data and software availability The physicochemical proprieties were determined via Heliquest server https://heliquest.ipmc.cnrs.fr/. Potential receptors were search using PharmMapper available in http://www.lilab-ecust.cn/pharmmapper/. Receptor sequence file was obtained from website protein data bank https://www.rcsb.org/. Molecular docking method was performed by PatchDock https://bioinfo3d.cs.tau.ac.il/PatchDock/. Ligand and receptor interaction, molecular presentation was building by free software UCSF chimera (version 1.16) https://www.cgl.ucsf.edu/chimera/. For prediction of ligand site, it was used I-TASSER (protein function & function prediction) server https://zhanggroup.org/I-TASSER/. All file used in this study are available in https://github.com/eliasseif/Oligoventin_prospecting.git. Acknowledgments We thank all the team of the Protein Chemistry Laboratory at the Laboratory for Applied Toxinology (LETA - Butantan Institute, Brazil) for the constant support and encouragement. Additionally, we thank the technicians Rosa Maria Carmo and Priscila do Nascimento Nanni. Author Contributions: Conceptualization, E.J.M.S. and P.I.S.J. ; methodology E.J.M.S. and P.I.S.J.; software, E.J.M.S. and P.I.S.J. ; validation, E.J.M.S. and P.I.S.J. ; formal analysis, E.J.M.S. and P.I.S.J. ; investigation, E.J.M.S. and P.I.S.J. ; resources, P.I.S.J. ; data curation, E.J.M.S. and P.I.S.J. ; writing-original draft preparation, E.J.M.S. ; writing, review and editing, E.J.M.S. and P.I.S.J. ; supervision, P.I.S.J. ; project administration, P.I.S.J.; funding acquisition, P.I.S.J. All authors have read and agreed to the published version of the manuscript. Funding: This research received financial support from the Research Support Foundation of the State of São Paulo (FAPESP/CeTICS), grant number 2013/07467-1, and from the Brazilian National Council for Scientific and Technological Development (CNPq), grant numbers 472744/2012-7 and 161722/2021-0. Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References Epand RM, Walker C, Epand RF, Magarvey NA. Molecular mechanisms of membrane targeting antibiotics. Biochim Biophys Acta - Biomembr [Internet]. 2016 [cited 2022 Jul 5];1858(5):980–7. Available from: https://www.sciencedirect.com/science/article/pii/S0005273615003582 Utama GL, Meliana S, Djali M, Yuliana T, Balia RL. Probiotic candidates yeast isolated from dangke–Indonesian traditional fermented buffalo milk. 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Supplementary Files TableS1.xlsx Table S1 TableS2.xlsx Table S2 TableS3.xlsx Table S3 TableS4.xlsx Table S4 Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4013832","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276324638,"identity":"b65caa7d-0cc3-48c9-9b0a-eeefb6397f70","order_by":0,"name":"Elias Jorge Muniz Seif","email":"","orcid":"https://orcid.org/0000-0001-9914-8897","institution":"Butantan Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Elias","middleName":"Jorge Muniz","lastName":"Seif","suffix":""},{"id":276325205,"identity":"57a160ed-219e-4516-ad12-cd6d5d9af8b1","order_by":1,"name":"Pedro Ismael da Silva Junior","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYDACZgYGA4aKAyhibERoOXOAgYeBgbGBOC0gwNhGihZzdvYHxZXz7iTuZz97/MHPHQx2/RIJbI8r8GixbOYxMDy77VliD09eYmPvGYbkmTMS2A3P4NFicJiHwbBx2+HEHoYcwwbeNoZkgzMH2CQb8Gphf2DYOAeohf+NYeNf4rQwGBg2NgC1SOQYNgNtsTM43oBfC9gvDceeGffceGM4W7ZNIkGyvbHdEJ8Wc/7jzwwbau7ItvfnGHx822Zjz8/MfOwhXocBY8EAiS+R2ICIH5xamB8gC9jjVT4KRsEoGAUjEgAAe5tO5jdIsiAAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-6619-6489","institution":"Butantan Institute","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"Ismael da Silva","lastName":"Junior","suffix":""}],"badges":[],"createdAt":"2024-03-04 18:23:12","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-4013832/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4013832/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52066261,"identity":"e6339241-5faf-4e2f-ad01-48ab89277a8f","added_by":"auto","created_at":"2024-03-06 06:52:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3783922,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular docking between Oligoventin and receptors. In (A) overview of interaction with Pyridoxine 5-phosphate synthase. In (B) overview of interaction with Threonine dehydratase biosynthetic. In (C) overview of interaction with Fumarate reductase flavoprotein subunit. In (D) overview of interaction with Cyclomaltodextrin glucanotransferase. Red brick (Oligoventin), Medium Blue (Receptor), Forest Green (predicted ligand bind site residues), golden yellow (literature bind site residues) yellow line (intramolecular forces) and White label (residue name and sequence).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/260a80f4d3b67b7cff9370f9.png"},{"id":52066791,"identity":"fbe02c9c-4dce-4e08-984c-274cbafa59ca","added_by":"auto","created_at":"2024-03-06 07:00:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2700743,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular docking between Oligoventin and receptors. In (A) focusses in Oligoventin and Thymidylate synthase thyX interaction. In (B) overview of interaction with Thymidylate synthase thyX. In (C) focusses in Oligoventin and Enoyl-ACP reductase interaction. In (D) overview of interaction with Enoyl-ACP reductase. Red brick (Oligoventin), Medium Blue (Receptor), Forest Green (predicted ligand bind site residues), golden yellow (literature bind site residues) yellow line (intramolecular forces) and White label (residue name and sequence).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/e43a84d64adad65982db48da.png"},{"id":52067554,"identity":"adc344aa-800c-44f8-b300-9eb3cdd7995d","added_by":"auto","created_at":"2024-03-06 07:16:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3176840,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/58e91a8a-8d8d-458f-bd0e-ac8ca1645aa8.pdf"},{"id":52066258,"identity":"68e58fa4-036a-484f-b710-793227a9456b","added_by":"auto","created_at":"2024-03-06 06:52:02","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15154,"visible":true,"origin":"","legend":"\u003cp\u003eTable S1\u003c/p\u003e","description":"","filename":"TableS1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/e26c3c8d3386750a0263e1c4.xlsx"},{"id":52067222,"identity":"c4346728-2260-45e3-8b4e-69176f38fdab","added_by":"auto","created_at":"2024-03-06 07:08:02","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":13864,"visible":true,"origin":"","legend":"\u003cp\u003eTable S2\u003c/p\u003e","description":"","filename":"TableS2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/cd245830c4dbbd640c25be8d.xlsx"},{"id":52066790,"identity":"a6ece8ae-b3a0-465f-b5a0-cf74e659b6b4","added_by":"auto","created_at":"2024-03-06 07:00:02","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":22920,"visible":true,"origin":"","legend":"\u003cp\u003eTable S3\u003c/p\u003e","description":"","filename":"TableS3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/7f99985cef437cc32a99d92c.xlsx"},{"id":52066256,"identity":"0c41ce19-d5ce-4b7c-a0cc-7108a872e097","added_by":"auto","created_at":"2024-03-06 06:52:01","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":69744,"visible":true,"origin":"","legend":"\u003cp\u003eTable S4\u003c/p\u003e","description":"","filename":"TableS4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4013832/v1/33cd40a4b34f2fbe850613c6.xlsx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIn silico\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e bioprospecting of receptors for Oligoventin: an antimicrobial peptide isolated from spider eggs of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003ePhoneutria nigriventer\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBacteria are unicellular organisms with an unstructured nucleus, known as prokaryotes. They are closely associated with human activities. In general, this association is beneficial to humanity (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, it can also be a disharmonious relationship, with parasitism being the main cause of disease (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Thus, microorganisms are also associated with impairments in agriculture, the food industry, and public health as: \u003cem\u003eSalmonella typhi\u003c/em\u003e (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), \u003cem\u003eStreptococcus pyogenes\u003c/em\u003e (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) \u003cem\u003eand Mycobacterium tuberculosis\u003c/em\u003e (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe emergence of microorganisms resistant to traditional drugs is increasing each year, primarily due to the irresponsible and widespread use of antimicrobial agents, coupled with the high mutational capacity of certain bacterial strains. Studies indicate that multidrug-resistant organisms may lead to the deaths of 10\u0026nbsp;million people per year by 2050, making it the leading cause of mortality in humans and resulting in an estimated expenditure of over \u003cspan\u003e$\u003c/span\u003e100 trillion on public health systems worldwide (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe development of new antimicrobial drugs is crucial in mitigating the impact caused by resistant organisms. Peptides or peptidic-derived biomolecules, which are amino acid polymers, offer an alternative to combating resistant organisms. Once these molecules are associated with antimicrobial activity, they exhibit a high capacity for analog production (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOligoventin (COOH-QPFSLERW-NH\u003csub\u003e2\u003c/sub\u003e) is a neutral and amphiphilic peptide isolated from spider eggs of \u003cem\u003ePhoneutria nigriventer\u003c/em\u003e. This molecule exhibits antimicrobial activity against Gram-positive bacteria (\u003cem\u003eMicococcus luteus, Staphylococcus aureus\u003c/em\u003e, and \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e) with minimal inhibitory concentrations (MIC) ranging from 47.2 to 188.9 \u0026micro;M (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Additionally, it demonstrates activity against Gram-negative strains (\u003cem\u003eSerratia marcescens\u003c/em\u003e) with MIC ranging from 25.7 to 47.2 \u0026micro;M (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Furthermore, it displays antifungal activity against \u003cem\u003eCandida albicans\u003c/em\u003e and \u003cem\u003eCandida auris\u003c/em\u003e, with MIC lower than 1 mM. However, the molecular target and mechanism of action of this peptide remain unknown.\u003c/p\u003e \u003cp\u003eComputational tools are currently utilized for simulating biological and physicochemical phenomena. These tools are commonly used in protein chemistry, enabling the evaluation of molecular three-dimensional structure, folding, interactions, docking, and dynamics (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). \u003cem\u003eIn silico\u003c/em\u003e methods offer the principal advantage of reducing the time and cost associated with screening assays.\u003c/p\u003e \u003cp\u003eTherefore, the aim of this study was to prospect receptors associated with the antimicrobial activity of the Oligoventin peptide using bioinformatics tools (\u003cem\u003ein silico\u003c/em\u003e).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e \u003cb\u003ePeptide Characterization and Folding\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTo determine the physicochemical parameters of the peptide (net charge, hydrophobicity, hydrophobic moment, and molecular weight), the amino acid sequence of Oligoventin (COOH-QPFSLERW-NH\u003csub\u003e2\u003c/sub\u003e) was submitted to the Heliquest server (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The three-dimensional structure and free energy minimization were performed using UCSF Chimera software (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) with the following settings: 1000 steps of steepest descent, steepest descent step size of 0.02 \u0026Aring;, 10 steps of conjugate gradient, conjugate gradient step size of 0.02 \u0026Aring;, update interval of 10, and no fixed atoms after hydrogen addition, hydrogen bond addition, charges, and side-chain torsion (using the amber force field ff14SB).\u003c/p\u003e\n\u003ch3\u003eTargets Prospection\u003c/h3\u003e\n\u003cp\u003eThe PharmMapper server was utilized to identify potential receptors for Oligoventin (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The Oligoventin structure was submitted to the server with the following parameters: Generate Conformers (YES), Maximum Generated Conformations (300), and full/complete pharmacophore mapping with all Targets selected (v2010, 7302), and a number of Reserved Matched Targets (300). The top 50 best-ranked targets based on normalized fit score were chosen, and further filtered by microbial origin (Gram-positive or Gram-negative). Consequently, 22 targets were selected for this study, and the structure of each target was downloaded from the Protein Data Bank (PDB) server.\u003c/p\u003e\n\u003ch3\u003eMolecular Docking\u003c/h3\u003e\n\u003cp\u003eThe PatchDock server was employed to conduct molecular docking between Oligoventin (ligand) and all 22 targets identified in PharmMapper (receptors) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). PatchDock server parameters were set to Clustering RMSD (4.0) and Complex Type (Default). For each receptor, the best solution (conformation) was determined by collecting Score, Area, ACE (effective atomic contact energies), and transformation value. Ultimately, the highest score value was used to assess the optimal binding of Oligoventin.\u003c/p\u003e\n\u003ch3\u003eLigand and Receptor interaction\u003c/h3\u003e\n\u003cp\u003eThe software UCSF Chimera was utilized to analyze the interaction between Oligoventin and the receptors (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The FindHBond tool was configured with relaxed constraints (2 \u0026Aring; and 20 degrees) to identify hydrogen bonds. Only hydrogen atoms with a distance of less than 4 \u0026Aring; between their heavy atoms were considered in this study. Additionally, information regarding electron donor/acceptor and residue interactions between the ligand and receptor was collected.\u003c/p\u003e\n\u003ch3\u003eLigand binding site prediction\u003c/h3\u003e\n\u003cp\u003eThe I-TASSER (protein function \u0026amp; function prediction) server was employed to identify binding sites for receptors (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In this study, only the top 6 receptors (based on major docking scores) were selected for analysis. For polymeric proteins, only one chain was used for this analysis. Subsequently, the predicted binding sites were compared with those found by docking analysis to assess the accuracy of receptor selection.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003ePeptide characterization\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOligoventin (COOH-QPFSLERW-NH2) is a neutral peptide with a net charge of 0, comprising 8 amino acids with a molecular weight of 1062.18 g/mol and an isoelectric point of pH 6.58. This peptide consists of half hydrophilic and half hydrophobic residues, with two of them being aromatic, resulting in an extinction coefficient of 5690 M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, indicating good water solubility. Additionally, \u003cem\u003ein silico\u003c/em\u003e energy minimization of the peptide structure yielded \u0026minus;\u0026thinsp;852.55 kJ/mol. This molecule was utilized to perform simulations in this study.\u003c/p\u003e\n\u003ch3\u003eTargets Prospection\u003c/h3\u003e\n\u003cp\u003eAfter performing the initial search on the PharmMapper server, 300 potential receptors were identified (Table S1). These were filtered by their origin from microorganisms (Gram-positive or Gram-negative), resulting in 22 targets with normalized fit scores ranging from 0.9912 to 0.9313 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe top three receptors based on their score are Urocanate hydratase (1W1U), Aspartate aminotransferase (1TOI), and Copper-containing nitrite reductase (1RZP), ranked as 3, 4, and 9, respectively, in the general rank. Conversely, the receptors with the lowest fit scores are A/G-specific adenine glycosylase (1WEI), 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (1U3L), and DNA protection during starvation protein 2 (1JI5), ranked as 50, 47, and 42, respectively, in the general rank (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePharmMapper search results using Oligoventin as a ligand\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePM\u003c/p\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePDB ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTarget Name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNormalized Fit Score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOrigin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGram\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1W1U\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUrocanate hydratase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9912\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ePseudomonas putida\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TOI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAspartate aminotransferase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1RZP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCopper-containing nitrite reductase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9817\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eAchromobacter cycloclastes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1SFJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3-dehydroquinate dehydratase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus aureus subsp. aureus MRSA252\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UDX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHypothetical protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eThermus thermophilus HB8\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1KSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFumarate reductase flavoprotein subunit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eShewanella frigidimarina\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1O28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThymidylate synthase thyX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9698\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eThermotoga maritima\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1LXC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEnoyl-ACP Reductase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1M5W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePyridoxine 5-phosphate synthase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9673\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1B6G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHaloalkane dehalogenase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eXanthobacter autotrophicus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UFY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChorismate mutase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eThermus thermophilus HB8\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UXG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalate dehydrogenase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eChloroflexus aurantiacus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1VMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCell division protein FtsY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9463\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eThermotoga maritima\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1Y54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBeta-lactamase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.946\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEnterobacter cloacae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1BO5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlycerol kinase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1VMK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePurine nucleoside phosphorylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eThermotoga maritima MSB8\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UKQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCyclomaltodextrin glucanotransferase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eBacillus sp. 1011\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TDJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThreonine dehydratase biosynthetic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9403\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2PIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFimbrial protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eNeisseria gonorrhoeae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1JI5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDNA protection during starvation protein 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9386\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eBacillus anthracis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1U3L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1WEI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G-specific adenine glycosylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePM Rank (General PharmMapper rank search), PDB ID (Identification code in protein data bank), Normalized Fit Score (value obtained by ratio of fit score and number of features), Origin (Specie form the target was isolated), + (Gram-positive), - (Gram-Negative).\u003c/p\u003e\n\u003ch3\u003eMolecular docking results\u003c/h3\u003e\n\u003cp\u003eDocking results showed a range of scores (10982 to 5308), areas (1493.9 to 679.9), and ACE values (289.21 to -290.26). The rankings obtained from the PatchDock server differed from those presented by PharmMapper. The complete results are provided in Table S2.\u003c/p\u003e \u003cp\u003eIn the molecular docking analysis, Thymidylate synthase ThyX (Id\u003csub\u003epdb\u003c/sub\u003e 1O28), Pyridoxine 5-phosphate synthase (Id\u003csub\u003epdb\u003c/sub\u003e 1M5W), Threonine dehydratase biosynthetic (Id\u003csub\u003epdb\u003c/sub\u003e 1TDJ), Enoyl-ACP reductase (Id\u003csub\u003epdb\u003c/sub\u003e 1LXC), Fumarate reductase flavoprotein subunit (1KSS), and Cyclomaltodextrin glucanotransferase (Id\u003csub\u003epdb\u003c/sub\u003e 1UKQ) exhibited top dock scores. Additionally, these targets showed similar interaction areas, ranging from 1492.9 to 881.2. However, targets 1TDJ (-2.33), 1LXC (-290.26), and 1KSS (-218.38) presented negative values for ACE (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn contrast, targets with lower dock scores included Fimbrial protein (Id\u003csub\u003epdb\u003c/sub\u003e 2PIL), Haloalkane dehalogenase (Id\u003csub\u003epdb\u003c/sub\u003e 1B6G), Chorismate mutase (Id\u003csub\u003epdb\u003c/sub\u003e 1UFY), and 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (Id\u003csub\u003epdb\u003c/sub\u003e 1U3L). All of these targets exhibited interaction areas less than 800 and positive values of ACE (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDocking results by PatchDock server. Oligoventin was used as ligand, and target obtained by PharmMapper was used as receptor.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePM\u003c/p\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePDB ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReceptor Name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eScore\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eArea\u003c/p\u003e \u003cp\u003e(\u0026Aring;\u0026sup2;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eACE\u003c/p\u003e \u003cp\u003e(Kcal/mol)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1O28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThymidylate synthase thyX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1493.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e289.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1M5W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePyridoxine 5-phosphate synthase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e999.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e255.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TDJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThreonine dehydratase biosynthetic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1072.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-2.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1LXC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEnoyl-ACP reductase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1105.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-290.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1KSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFumarate reductase flavoprotein subunit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7776\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1238.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-218.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UKQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCyclomaltodextrin glucanotransferase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7698\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e881.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e114.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1BO5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlycerol kinase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7640\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e139.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1VMK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePurine nucleoside phosphorylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e882.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e276.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1RZP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCopper-containing nitrite reductase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7286\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e837.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UXG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalate dehydrogenase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e921.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-126.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UDX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHypothetical protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e930.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-195.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TOI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAspartate aminotransferase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e886.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-136.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1Y54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBeta-lactamase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e928.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e43.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1W1U\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUrocanate hydratase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6824\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1033.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e210.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1WEI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G-specific adenine glycosylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e858.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-24.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1VMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCell division protein FtsY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6614\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e792.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e184.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1JI5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDNA protection during starvation protein 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e798.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e248.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1SFJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3-dehydroquinate dehydratase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e765.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-73.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1U3L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e661.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e99.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UFY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChorismate mutase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5696\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e721.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e108.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1B6G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHaloalkane dehalogenase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e770.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e102.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2PIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFimbrial protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e697.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e28.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePM Rank (General PharmMapper rank search), PDB ID (Identification code in protein data bank), ACE (Atomic efective contact energy - Kcal/mol)\u003c/p\u003e\n\u003ch3\u003eReceptor and ligand binding analysis\u003c/h3\u003e\n\u003cp\u003eTo simplify the analysis, only hydrogen bonds (\u0026le;\u0026thinsp;4\u0026Aring;) were considered in the docking results, and the entire binding interactions are summarized in Table S3. In all interactions observed, Oligoventin acted as the electron donor, while the receptor served as the acceptor. No association was found between the number of hydrogen bonds and the dock score.\u003c/p\u003e \u003cp\u003eThymidylate synthase ThyX (4 bonds) exhibited interactions among HIS5.L -\u0026gt; Thr\u003csub\u003e101.RB\u003c/sub\u003e, Gln1.L -\u0026gt; Glu\u003csub\u003e58RA\u003c/sub\u003e / Thr\u003csub\u003e161.RB\u003c/sub\u003e, and Arg\u003csub\u003e7.L\u003c/sub\u003e -\u0026gt; Glu\u003csub\u003e54.RA\u003c/sub\u003e. Pyridoxine 5-phosphate synthase and Threonine dehydratase biosynthetic showed 1 bond each, with receptor Gln\u003csub\u003e1.L\u003c/sub\u003e -\u0026gt; Glu\u003csub\u003e240.RD\u003c/sub\u003e and Gln\u003csub\u003e1.L\u003c/sub\u003e -\u0026gt; Glu\u003csub\u003e324.R\u003c/sub\u003e, respectively. Finally, Enoyl-ACP reductase (3 bonds) demonstrated interactions among Gln\u003csub\u003e1.L\u003c/sub\u003e -\u0026gt; Gly\u003csub\u003e13.RB\u003c/sub\u003e / Ser\u003csub\u003e19.RB\u003c/sub\u003e and Arg\u003csub\u003e7.L\u003c/sub\u003e -\u0026gt; ILE\u003csub\u003e192.RB\u003c/sub\u003e (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHydrogens H-Bond (\u0026le;\u0026thinsp;4\u0026Aring;) between receptor and Oligoventin obtained by a docking result of Patchdock Server\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePM\u003c/p\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePDB ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReceptor Name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDonor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAcceptor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eD-A distance (\u0026Aring;)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1O28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThymidylate synthase thyX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHIS 5.L NE2\u003c/p\u003e \u003cp\u003eGLN 1.L NE2\u003c/p\u003e \u003cp\u003eGLN 1.L NE2\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTHR 101.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eGLU 58.R\u003csub\u003eA\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eTHR 161.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eGLU 54.R\u003csub\u003eA\u003c/sub\u003e OE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.717\u003c/p\u003e \u003cp\u003e3.850\u003c/p\u003e \u003cp\u003e3.875\u003c/p\u003e \u003cp\u003e3.426\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1M5W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePyridoxine 5-phosphate synthase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLU 240.R\u003csub\u003eD\u003c/sub\u003e OE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.394\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TDJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThreonine dehydratase biosynthetic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLU 324.R OE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1LXC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEnoyl-ACP Reductase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003cp\u003eARG 7.L NE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLY 13.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eSER 19.R\u003csub\u003eB\u003c/sub\u003e OG\u003c/p\u003e \u003cp\u003eILE 192.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.964\u003c/p\u003e \u003cp\u003e2.872\u003c/p\u003e \u003cp\u003e3.705\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1KSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFumarate reductase flavoprotein subunit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UKQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCyclomaltodextrin glucanotransferase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L NE2\u003c/p\u003e \u003cp\u003eGLN 1.L NE2\u003c/p\u003e \u003cp\u003eARG 7.L NE\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTYR 406.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eGLY 502.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eTHR 409.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eTHR 409.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.764\u003c/p\u003e \u003cp\u003e2.401\u003c/p\u003e \u003cp\u003e3.795\u003c/p\u003e \u003cp\u003e3.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1BO5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlycerol kinase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePHE 3.L N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTHR 14.R\u003csub\u003eA\u003c/sub\u003e OG1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.528\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1VMK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePurine nucleoside phosphorylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L NE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eARG 140.R\u003csub\u003eC\u003c/sub\u003e O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1RZP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCopper-containing nitrite reductase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UXG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalate dehydrogenase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLY 79.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.810\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UDX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHypothetical protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 7.L NH1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eALA 368.R O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.872\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TOI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAspartate aminotransferase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTHR 59.R O\u003c/p\u003e \u003cp\u003eTYR 288.R O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.486\u003c/p\u003e \u003cp\u003e3.441\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1Y54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBeta-lactamase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003cp\u003eSER 4.L OG\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSER 310.R OG\u003c/p\u003e \u003cp\u003eSER 281.R OG\u003c/p\u003e \u003cp\u003eASP 280.R OD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.763\u003c/p\u003e \u003cp\u003e3.649\u003c/p\u003e \u003cp\u003e3.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1W1U\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUrocanate hydratase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSER 4.L OG\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eASN 6.R\u003csub\u003eA\u003c/sub\u003e OD1\u003c/p\u003e \u003cp\u003eASN 6.R\u003csub\u003eA\u003c/sub\u003e OD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.263\u003c/p\u003e \u003cp\u003e3.908\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1WEI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G-specific adenine glycosylase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLN 33.R OE1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1VMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCell division protein FtsY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSER 4.L N\u003c/p\u003e \u003cp\u003eARG 7.L NH1\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLN 1.L O\u003c/p\u003e \u003cp\u003eASN 80.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003cp\u003eASN 80.R\u003csub\u003eB\u003c/sub\u003e O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.847\u003c/p\u003e \u003cp\u003e3.423\u003c/p\u003e \u003cp\u003e3.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1JI5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDNA protection during starvation protein 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePHE 36.RA O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.504\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1SFJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3-dehydroquinate dehydratase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTYR 15.R\u003csub\u003eB\u003c/sub\u003e OH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.327\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1U3L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eASP 55.R OD2\u003c/p\u003e \u003cp\u003eASP 38.R OD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.453\u003c/p\u003e \u003cp\u003e3.435\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UFY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChorismate mutase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1B6G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHaloalkane dehalogenase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 7.L NH2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGLN 181.R O\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.858\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2PIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFimbrial protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 1.L N\u003c/p\u003e \u003cp\u003eARG 7.L NE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTRP 111.R O\u003c/p\u003e \u003cp\u003eASP 145.R OD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.641\u003c/p\u003e \u003cp\u003e3.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDonor (Electron donor residue), Acceptor (Electron acceptor residue), D-A distance (distance between heavy atoms of electron acceptor and donor), GLY 1.L N (Residue name/ Number/ Chain ID/ Shared electron atom), L (Ligand ID), Rx (ReceptorSubunit ID)\u003c/p\u003e\n\u003ch3\u003eReceptor and ligand binding analysis\u003c/h3\u003e\n\u003cp\u003eLigand binding site predictions were conducted for the six receptors with the highest dock scores. The major C-Scores are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, while all ligand site predictions can be found in Table S4.\u003c/p\u003e \u003cp\u003eReceptors 1O28 (Score\u0026thinsp;=\u0026thinsp;0.42; Size\u0026thinsp;=\u0026thinsp;45), 1M5W (Score\u0026thinsp;=\u0026thinsp;0.93; Size\u0026thinsp;=\u0026thinsp;141), 1TDJ (Score\u0026thinsp;=\u0026thinsp;0.97; Size\u0026thinsp;=\u0026thinsp;200), 1KSS (Score\u0026thinsp;=\u0026thinsp;0.88; Size\u0026thinsp;=\u0026thinsp;128), and 1UKQ (Score\u0026thinsp;=\u0026thinsp;0.86; Size\u0026thinsp;=\u0026thinsp;108) did not exhibit co-location between predicted and docked residues. Only receptor 1LXC (Score\u0026thinsp;=\u0026thinsp;0.86; Size\u0026thinsp;=\u0026thinsp;702) shared residues between both models. The co-localized residues were 13, 19, 91, 192, and 194 (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBind site co-location among predicted (I-TASSER), found in study (PatchDock) and literature descripted. Only one protein chain was used in this analysis. In \u003cb\u003ebold\u003c/b\u003e residue shared for bind site models.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePM\u003c/p\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePDB ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCluster Score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCluster size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLigand bind site residues (Prediction)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLigand bind site residues (Found)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1O28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42, 65, 67, 70, 93, 175, 177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39,40, 54ra,54ra, 163ra, 163rc, 165ra, 165rc, 169rc, 172rc 211ra, 211rc, 211rc\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1M5W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72, 94, 133, 153, 192, 193, 194, 213, 214, 215, 216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e228ra, 228ra, 235rf, 236rf, 236rg, 236rg, 240rd,\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1TDJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60, 61, 62, 87, 88, 89, 90, 157, 186, 188, 189, 190, 191, 192, 241, 242, 286, 288, 315, 316\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e320r, 320r, 321r, 323r, 324r, 458r, 461r\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1LXC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e704\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e13\u003c/b\u003e, 15, 16, \u003cb\u003e19\u003c/b\u003e, 20, 39, 40, 41, 63, 64, 65, \u003cb\u003e91\u003c/b\u003e, 92, 93, 94, 119, 144, 145, 146, 159, 163, 189, 190, 191, \u003cb\u003e192\u003c/b\u003e, \u003cb\u003e194\u003c/b\u003e, 195, 196, 197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e13rb\u003c/b\u003e, \u003cb\u003e19rb\u003c/b\u003e, \u003cb\u003e91rb\u003c/b\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), 97rb, \u003cb\u003e192rb\u003c/b\u003e, \u003cb\u003e194rb\u003c/b\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1KSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e132, 133, 134, 135, 136, 137, 156, 157, 158, 162, 163, 164, 165, 167, 168, 169, 170, 171, 276, 277, 278, 312, 313, 314, 336, 337, 338, 344, 375, 504, 505, 533, 534, 544, 547, 548, 549, 550, 553\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44r, 52r, 53r(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), 74r, 423r, 426r\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1UKQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100, 140, 194, 197, 227, 229, 230, 257, 327, 328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e311rb(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), 406rb(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), 409rb(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), 424rb, 502rb, 576rb,\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eCluster Score\u003c/b\u003e (confidence score of the prediction, ranges [0\u0026ndash;1]), \u003cb\u003eCluster size\u003c/b\u003e (total number of templates in a cluster).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe principal molecular pathways of antimicrobial molecules involve the impairment of protein, lipid, cell wall, genetic material synthesis, and membrane injury (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Cationic amphiphilic peptides primarily exert their action mechanism through membrane interaction and disruption (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). This occurs due to their physicochemical properties; the positively charged peptide is attracted to the negatively charged bacterial plasma membrane (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Subsequently, its amphiphilic characteristics enable the peptide to embed into the bacterial membrane, forming toroidal pores, barrel-stave pores, or carpet-like structures, leading to electrolytic imbalance and ultimately cell death (\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). However, this mechanism is not specific, and cationic peptides are potentially cytotoxic (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, some peptides interact with intracellular targets, inhibiting protein (e.g., Pleurocidin, Apidaecin Hb1a), lipid (e.g., Mersacidin, MBI-28), and DNA (e.g., Buforin II, Ostricacin-1) biosynthesis, thereby harming microbial development (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The Heliquest results showed that Oligoventin is a neutral and hydrophilic peptide. Furthermore, experimental assays demonstrated that this peptide does not exhibit cytotoxicity against fresh human blood cells at a concentration of 500\u0026micro;M (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Both results suggest that the antimicrobial activity of Oligoventin is associated with intracellular pathways, interfering with bacterial homeostasis.\u003c/p\u003e \u003cp\u003ePharmMapper is an online reverse docking tool that identifies targets using a mapping approach. After conducting the necessary methodology, 22 potential receptors for Oligoventin originating from both Gram-positive and Gram-negative microorganisms were identified. Subsequently, molecular docking was performed using PatchDock, revealing the best targets as thymidylate synthase ThyX (Id\u003csub\u003epdb\u003c/sub\u003e 1O28), pyridoxine 5-phosphate synthase (Id\u003csub\u003epdb\u003c/sub\u003e 1M5W), threonine dehydratase biosynthetic (Id\u003csub\u003epdb\u003c/sub\u003e 1TDJ), enoyl-ACP reductase (Id\u003csub\u003epdb\u003c/sub\u003e 1LXC), fumarate reductase flavoprotein subunit (Id\u003csub\u003epdb\u003c/sub\u003e 1KSS), and cyclomaltodextrin glucanotransferase (Id\u003csub\u003epdb\u003c/sub\u003e 1UKQ).\u003c/p\u003e \u003cp\u003eMoreover, only receptors 1LXC and 1TDJ exhibited negative ACE values, suggesting thermodynamically favorable interactions between Oligoventin and these receptors (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Notably, only enoyl-ACP reductase (Id\u003csub\u003epdb\u003c/sub\u003e 1LXC) showed co-localization between the docked and ligand site predicted by I-TASSER (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThymidylate synthase ThyX is an enzyme implicated in prokaryotic cell DNA synthesis, with two principal sites: the FAD\u003csup\u003e+\u003c/sup\u003e cofactor site (Asn\u003csub\u003e16\u003c/sub\u003e, Ser\u003csub\u003e30\u003c/sub\u003e, Thr\u003csub\u003e55\u003c/sub\u003e, His\u003csub\u003e79\u003c/sub\u003e, Glu\u003csub\u003e86\u003c/sub\u003e, and Arg\u003csub\u003e165\u003c/sub\u003e) and the dUMP substrate site (Arg\u003csub\u003e78\u003c/sub\u003e, Glu\u003csub\u003e86\u003c/sub\u003e, Ser\u003csub\u003e88,\u003c/sub\u003e Arg\u003csub\u003e90\u003c/sub\u003e, Arg\u003csub\u003e147\u003c/sub\u003e and Arg\u003csub\u003e174\u003c/sub\u003e,) (\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). The dock simulation revealed co-localization with Arg\u003csub\u003e165\u003c/sub\u003e, present in the FAD\u003csup\u003e+\u003c/sup\u003e cofactor site. However, no residues were co-localized with the predicted site from the I-TASSER server (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u0026ndash; \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Despite this, this receptor was discarded as a potential molecular target for Oligoventin due to the positive ACE value, indicating that the interaction is thermodynamically unfavorable \u003cem\u003ein vitro\u003c/em\u003e assays.\u003c/p\u003e \u003cp\u003ePyridoxine 5-phosphate synthase is an enzyme associated with B6 vitamin synthesis, serving as an important cofactor in amino acid metabolism and glycogenolysis. This enzyme forms a complex with 1-deoxy-D-xylulose phosphate (dXP), involving residues such as Asp\u003csub\u003e11\u003c/sub\u003e, His\u003csub\u003e12\u003c/sub\u003e, Arg\u003csub\u003e20,\u003c/sub\u003e His\u003csub\u003e52\u003c/sub\u003e, Glu\u003csub\u003e72\u003c/sub\u003e, Thr\u003csub\u003e103\u003c/sub\u003e, Glu\u003csub\u003e153\u003c/sub\u003e, and His\u003csub\u003e193\u003c/sub\u003e (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). While the dock simulation did not reveal shared residues with the dXP site, the predicted model exhibited co-localization with Glu\u003csub\u003e153\u003c/sub\u003e, Glu\u003csub\u003e72\u003c/sub\u003e and His\u003csub\u003e193\u003c/sub\u003e (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003eThreonine dehydratase biosynthetic is an important enzyme in the biosynthesis of the amino acid threonine in E. coli. This structure contains a Pyridoxal 5-phosphate (PLP) binding site composed of Phe\u003csub\u003e61\u003c/sub\u003e, Lys\u003csub\u003e62\u003c/sub\u003e, Asn\u003csub\u003e89\u003c/sub\u003e, Gly\u003csub\u003e241\u003c/sub\u003e and Ser\u003csub\u003e315\u003c/sub\u003e (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Although the dock simulation did not reveal shared residues with PLP, all residues were shared with the predicted binding site (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003eEnoyl-ACP reductase is a key enzyme in the final step of type II fatty acid synthesis, specifically in the elongation phase. This molecule contains a cofactor binding site, with one binding site for NAD\u0026thinsp;+\u0026thinsp;comprising residues Ala\u003csub\u003e16\u003c/sub\u003e, Ala\u003csub\u003e41\u003c/sub\u003e, Leu\u003csub\u003e45\u003c/sub\u003e, Asp\u003csub\u003e67\u003c/sub\u003e, Val\u003csub\u003e68\u003c/sub\u003e, Ile\u003csub\u003e95\u003c/sub\u003e, and Ile\u003csub\u003e121\u003c/sub\u003e and another for the nicotinamide ring comprising Thr\u003csub\u003e147\u003c/sub\u003e, Tyr\u003csub\u003e148\u003c/sub\u003e, Ala\u003csub\u003e191\u003c/sub\u003e, Gly\u003csub\u003e192\u003c/sub\u003e, and Ile\u003csub\u003e194\u003c/sub\u003e (\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Both the dock simulation and predicted site revealed co-location with the residues Gly\u003csub\u003e192\u003c/sub\u003e and Ile\u003csub\u003e194\u003c/sub\u003e, which are present in the nicotinamide ring binding site (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec \u0026ndash; \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed).\u003c/p\u003e \u003cp\u003eFumarate reductase flavoprotein subunit is enzyme associated with bacteria respiration in oxygen absence, which are closely related to succinate dehydrogenase. This molecule has FAD\u003csup\u003e+\u003c/sup\u003e cofactor site (Glu\u003csub\u003e534\u003c/sub\u003e) and subtracts (His\u003csub\u003e504\u003c/sub\u003e) (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). Both residues not associated with Oligoventin in dock simulation results. In contrast, they are present in predicted binding site (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003eCyclomaltodextrin glucanotransferase is enzyme associated to carbohydrates metabolism, important in cyclization of D-glucose. The substrate site is formed by Tyr\u003csub\u003e100\u003c/sub\u003e, Phe\u003csub\u003e183\u003c/sub\u003e, Tyr\u003csub\u003e195\u003c/sub\u003e, Asp\u003csub\u003e229\u003c/sub\u003e, Phe\u003csub\u003e259\u003c/sub\u003e and Asp\u003csub\u003e328\u003c/sub\u003e (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Dock simulation not shows shared residues with substrate site, however Asp229 residues was shared with predicted bind site (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed).\u003c/p\u003e \u003cp\u003eTherefore, molecular docking simulations suggest that Oligoventin interacts more strongly with Enoyl-ACP reductase (Id\u003csub\u003epdb\u003c/sub\u003e 1LXC) and with less avidity with Thymidylate synthase ThyX (Id\u003csub\u003epdb\u003c/sub\u003e 1O28), potentially disrupting the normal functions of these enzymes. This interaction could lead to a decrease in fatty acid and DNA biosynthesis, ultimately reducing microbial proliferation and impacting bacterial homeostasis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe \u003cem\u003ein silico\u003c/em\u003e bioprospecting of receptors for the antimicrobial activity of Oligoventin proved to be highly efficient, identifying only two targets from a database containing over seven thousand enzymes. The integration of software tools, including PharmMapper for target search, PatchDock for molecular docking, I-TASSER for ligand site prediction, and literature validation, was instrumental in validating each step of the analysis.\u003c/p\u003e \u003cp\u003eIn this study, Enoyl-ACP reductase and Thymidylate synthase ThyX emerged as the most promising targets, showing consistent results across docking, prediction, and literature binding sites. These enzymes are associated with fatty acid and DNA synthesis in prokaryotic organisms. Thus, Oligoventin's interaction with these targets may disrupt their normal function by competing for cofactor or substrate binding sites, ultimately reducing microbial proliferation and leading to bacterial death, consistent with previous antibacterial in vitro assays.\u003c/p\u003e \u003cp\u003eThis study paves the way for further research into the interaction between receptors and ligands using molecular dynamics (\u003cem\u003ein silico\u003c/em\u003e) or enzymology assays (\u003cem\u003ein vitro\u003c/em\u003e). Furthermore, it suggests the potential for designing new Oligoventin analogs to enhance antimicrobial efficacy and explore other biological potentials, such as antitumoral and anti-inflammatory properties.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData and software availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe physicochemical proprieties were determined via Heliquest server\u0026nbsp;https://heliquest.ipmc.cnrs.fr/. Potential receptors were search using PharmMapper available in\u0026nbsp;http://www.lilab-ecust.cn/pharmmapper/. Receptor sequence file was obtained from website protein data bank\u0026nbsp;https://www.rcsb.org/. Molecular docking method was performed by PatchDock\u0026nbsp;https://bioinfo3d.cs.tau.ac.il/PatchDock/. Ligand and receptor interaction, molecular presentation was building by free software UCSF chimera (version 1.16)\u0026nbsp;https://www.cgl.ucsf.edu/chimera/. For prediction of ligand site, it was used I-TASSER (protein function \u0026amp; function prediction) server\u0026nbsp;https://zhanggroup.org/I-TASSER/. All file used in this study are available in\u0026nbsp;https://github.com/eliasseif/Oligoventin_prospecting.git.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the team of the Protein Chemistry Laboratory at the Laboratory for Applied Toxinology (LETA - Butantan Institute, Brazil) for the constant support and encouragement. Additionally, we thank the technicians Rosa Maria Carmo and Priscila do Nascimento Nanni.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConceptualization, E.J.M.S. and P.I.S.J. ; methodology E.J.M.S. and P.I.S.J.; software, E.J.M.S. and P.I.S.J. ; validation, E.J.M.S. and P.I.S.J. ; formal analysis, E.J.M.S. and P.I.S.J. ; investigation, E.J.M.S. and P.I.S.J. ; resources, P.I.S.J. ; data curation, E.J.M.S. and P.I.S.J. ; writing-original draft preparation, E.J.M.S. ; writing, review and editing, E.J.M.S. and P.I.S.J. ; supervision, P.I.S.J. ; project administration, P.I.S.J.; funding acquisition, P.I.S.J. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research received financial support from the Research Support Foundation of the State of S\u0026atilde;o Paulo (FAPESP/CeTICS), grant number 2013/07467-1, and from the Brazilian National Council for Scientific and Technological Development (CNPq), grant numbers 472744/2012-7 and 161722/2021-0.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eEpand RM, Walker C, Epand RF, Magarvey NA. Molecular mechanisms of membrane targeting antibiotics. 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Available from: https://pubmed.ncbi.nlm.nih.gov/14769878/\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"f5eb43b1-3ae1-4a68-a403-230b6ec9211a","identifier":"10.13039/501100001807","name":"Fundação de Amparo à Pesquisa do Estado de São Paulo","awardNumber":"CEPID/CeTICS 2013/07467-1","order_by":0},{"identity":"16404b64-f67b-4523-a22c-3031a37b5ff7","identifier":"10.13039/501100003593","name":"Conselho Nacional de Desenvolvimento Científico e Tecnológico","awardNumber":"472744/2012-7","order_by":1},{"identity":"a134f9fa-7382-4055-b621-147b5639d5c5","identifier":"10.13039/501100003593","name":"Conselho Nacional de Desenvolvimento Científico e Tecnológico","awardNumber":"161722/2021-0","order_by":2}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Instituto Butantan","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Computational Biology, Molecular Docking Simulation, Protein Domains, DNA Metabolism Enzymes","lastPublishedDoi":"10.21203/rs.3.rs-4013832/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4013832/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIrresponsible and wholesale use of antimicrobial agents is the principal cause of the emergence of strains of resistant microorganisms to traditional drugs. Oligoventin is a neutral peptide isolated from spider eggs of \u003cem\u003ePhoneutria nigriventer\u003c/em\u003e, with antimicrobial activity against Gram-positive, Gram-negative, and yeast organisms. However, the molecular target and pathways of antimicrobial activity are still unknown. Thus, the aim of the present study is to prospect receptors associated with the antimicrobial activity of Oligoventin using \u003cem\u003ein silico\u003c/em\u003e tools.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe PharmMapper server was used to prospect targets originating from microorganisms. Additionally, the PatchDock server was utilized to perform molecular docking between Oligoventin and the targets. Subsequently, the I-TASSER server was adopted to predict the ligand site. Finally, the docking results and predicted sites were compared with literature sites of each target.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty-two potential receptors for Oligoventin were identified. Among these, Enoyl-ACP reductase (Id\u003csub\u003epdb\u003c/sub\u003e1lxc) and Thymidylate synthase ThyX (Id\u003csub\u003epdb\u003c/sub\u003e 1O28) demonstrated superior interaction with the peptide, exhibiting co-localization between docked residues and literature sites. These enzymes play a crucial role in fatty acid and DNA biosynthesis in prokaryotes\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTherefore, \u003cem\u003ein silico\u003c/em\u003e results suggest that Oligoventin can impair fatty acid and DNA synthesis, thereby reducing microbial proliferation and causing microorganism death.\u003c/p\u003e","manuscriptTitle":"In silico bioprospecting of receptors for Oligoventin: an antimicrobial peptide isolated from spider eggs of Phoneutria nigriventer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-06 06:51:57","doi":"10.21203/rs.3.rs-4013832/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d3c6b3ef-c569-4096-9fef-cb53be4bba2b","owner":[],"postedDate":"March 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29126286,"name":"Bioinformatics"},{"id":29126287,"name":"Applied Biochemistry"}],"tags":[],"updatedAt":"2024-04-03T11:44:00+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-06 06:51:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4013832","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4013832","identity":"rs-4013832","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}