In-silico toxicity analysis for interaction between Organophosphates and Acetyl cholinesterase through molecular level simulation

In-silico toxicity analysis for interaction between Organophosphates and Acetyl cholinesterase through molecular level simulation | 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 toxicity analysis for interaction between Organophosphates and Acetyl cholinesterase through molecular level simulation Tanya Singh, Awadhesh Kumar Verma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5622034/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 Organophosphates act as the chief constituents of pesticides and nerve agents, and their toxicological effects have caused harm not just to our environment but to human beings as well. Here, we have observed how interaction of Organophosphates (OPs) with the synaptic enzyme Acetylcholinesterase (AChE) can provide effective insights into studying the biological manifestation of OPs causing human ailments like neurodegenerative diseases. To further analyze how these OP components when bound with functional enzymes in the human body induce neurodegenerative disorders, we present an in-silico analysis of the toxicity of Organophosphates (OPs) by their interaction with Acetyl cholinesterase (AChE), the enzyme responsible for regulating neuronal signalling and transmission among muscles and motor nerves. Computational analysis was done using molecular docking and density functional theory (DFT) approaches, where molecular docking simulations helped determine the binding affinity evaluation, interaction sites, and conformations of AChE when docked with OPs. DFT estimations explored molecular mechanisms for OP toxicity, electronic properties and reactivity of OP compounds selectively. Through docking results, relatively strong binding affinities between OPs and AChE was observed which suggested OPs potential interference with the enzyme's function. The molecular dynamics simulations for their interaction provided important insights for the molecular basis of organophosphate toxicity, emphasizing the importance of their interaction with neuronal functioning enzymes. Such computational approach could provide a valuable framework for OP toxicology prediction, along with further analysis for in-vitro and in-vivo experiments. Bioinformatics Computational Biology Molecular Biology Toxicology Neurology Scientific Communication Organophosphates Acetyl cholinesterase Molecular Docking Density Function Theory Toxicity. Figures Figure 1 Figure 2 Figure 3 1. Introduction Being the ester form of alcohol and phosphorus group and composed of varying organic compounds, organophosphates (OP) have exclusively been used in the manufacture and production of pesticides and insecticides, chemical agents for industrial applications and as nerve agents for biochemical hazard [ 1 ]. They have lately emerged as potential toxicogenic components affecting the sustainability of humans and the environment of our earth. Initially, these were developed to target pests and insects responsible for harming crops, by affecting their nervous system through neurotoxic effects and causing long-term damage or death to the encroachers [ 2 ]. But due to their excessive use in agricultural and industrial sectors, their effects are now being observed in the form of environmental pollution through biomagnification in aquatic food webs [ 3 ], soil leaching causing groundwater pollution and harm to terrestrial life, and through air pollution which is directly or indirectly affecting the health of animals and human beings [ 4 ]. The condition of acute poisoning caused by OPs involve twitching of muscles, respiratory difficulties, seizures, insomnia, temporary dementia and confusion [ 5 ]. Chronic toxicity effects can have long-term impacts such as neurodegenerative disorders, bronchorrhea and lung paralysis, damage to liver, kidneys and other vital organs, certain carcinogenic effects and even death in fatal cases [ 6 ]. Ongoing research is being conducted for pest control mechanisms to be less toxic, and implementation of strict rules and regulations for use of OPs for sustaining our living and our environment. Among humans, these compounds have been modified with fluoride and sulphur constituents to make nerve agents, for causing intentional harm for the purpose of chemical warfare or chemo-terrorism [ 7 ]. They could be in odourless liquid form to be used as aerosol sprays, or are combined with other chemicals for increasing their shelf life for prolonged toxic use. More efforts are being made in formulating antidotes against these nerve agents, and for that context their chemical framework is needed to be understood, how these components are made to induce rapid action and high toxic effects along with maintaining their stable nature by design [ 8 ]. Acetylcholinesterase (AChE) is an important functional enzyme present in an organism's nervous system (the brain, the spinal cord, and neuro-muscular junctions) [ 9 ], whose primary purpose is to break down acetylcholine (ACh), a neurotransmitter responsible for transmitting and ceasing nerve signals from synaptic gap of neurons to the motor nerves, and letting the muscles and nerve cells to relax and reset to combat spontaneous activation [ 10 ]. ACh tends to bind with the enzyme's activation region or site, which compels the neurotransmitter to act as catalyst in the process of hydrolyzation and convert into choline and acetate (Acetyl CoA). Such process is important for stimulation of brain activity and preventing muscle over-exhaustion at the same time [ 11 ]. The main target of OPs is to inhibit the working of AChE, where due to their interaction, ACh starts accumulating in the synapse gap, which deregulates the stimulation of motor nerve cells and muscles, causing a spontaneous cycle of hyper stimulation [ 12 ]. This can cause muscle cramping, distress to neural and circulatory networks, contraction of muscles around the lungs causing distress and difficulty breathing, which in turn can lead to paralytic shock. Through the process of phosphorylation, the inhibition of AChE done by OPs help influence in their toxic effect. The first step involves binding , where the combination of OPs with AChE makes a covalent bond with serine (Ser) amino acid at the active site [ 13 ]. The second step involves inactivation of AChE , where the process of phosphorylation causes inactivation of the enzyme and prevents it from breaking down ACh [ 14 ]. In the third step, ACh accumulation in the synapse caused by inhibition of AChE causes rapid stimulation of synaptic receptors. Then, finally the process of overstimulation of nerve cells causes deregulation of nerve signals which leads to acute to chronic symptoms in the nervous system, further affecting the brain and other vital organs [ 15 ]. Some vital studies have demonstrated the interaction of AChE and organophosphates, and how its inhibitory activity can be analysed at molecular level. One such study incorporated observations for interaction of OPs with AChE and Butyrylcholinesterase (BChE) where they demonstrated that the pesticide OP Ethoprophos showed more binding affinity property and had more inhibition towards AChE than BChE; and they also did the comparison of reactivators RS194B, 2-PAM and HI-6 for AChE, where the authors observed that RS194B had shown to be an effective reactivator for AChE [ 16 ]. Another study reviewed about the effects of OPs on different esterases where through a quantum mechanics molecular docking approach they studied the effects of aging on AChE by Sarin, Mipafox and Diisopropyl fluorophosphate (DFP), and they deduced that the complex of AChE with Mipafox had the highest energy barrier for aging process [ 17 ]. In a clinical case study, the authors tried to analyze tolerance level of enteral nutrition among OP poisoned patients who were on mechanical ventilation while being administered atropine, which is considered the main antidote for OP toxicity. They concluded that nutritional support is needed as part of toxicity removal and comprehensive therapy and can be integrated further in rehabilitation of patients suffering from effects of OP poisoning [ 18 ]. Our objective would be to focus on giving a comparative analysis on the interactions of different components of Organophosphates with AChE at molecular level and whether their interactions would differ from each other respectively in terms of bonding and interaction with the binding site, along with emphasis on harmful effects of these components on human health [ 19 ]-[ 21 ]. 2. Methodology 2.1 Theoretical modeling and Optimization of Organophosphates as Ligand molecules The three-dimensional (3D) theoretical modeling of 23 types of Organophosphates (Pesticides: Azamethiphos, Azinphos-methyl, Chlorpyrifos, Diazinon, Dichlorvos, Ethion, Fenitrothion, Malathion, Parathion, Methyl-parathion, Phosmet, Tetrachlorvinphos; Nerve agents: Sarin, Soman, Tabun, VX; Industrial/Medical chemicals: Disulfoton, Echothiophate, Ethoprophos, Isoflurophate, Tribufos, Trichlorfon and Tricresyl phosphate ) was conducted using the Marvin Sketch software [ 22 ]. The molecular structures were initially refined in both two-dimensional (2D) and 3D forms. Following this, structural validation was performed using Marvin View to ensure accurate 3D conformational integrity. Subsequently, the geometries of the organophosphate molecules were optimized to their respective transition states, with energy minimization carried out in multiple stages. Intermediate energy minimizations were executed utilizing ChemDraw and Chem3DPro software, ensuring a progressive refinement of the molecular geometries [ 23 ],[ 24 ]. For the feature DFT (Density Functional Theory), the Gaussian 09 package was used to obtain the eventual optimization for the molecules. The DFT calculations employed the RB3LYP functional in combination with the 6-311G basis set, offering a high level of computational accuracy for electronic structure calculations [ 25 ],[ 26 ]. The optimized molecular geometries were later tried for molecular docking analysis to investigate respective interactions between the organophosphate compounds and acetylcholinesterase (AChE), a key enzyme for acetylcholine transport from neurons to muscles for inducing contraction and relaxation [ 27 ]. The docking analysis provided insights into the binding affinities and interaction patterns between the ligands and AChE. 2.2 Preparation of AChE as Receptor molecule The three-dimensional structure for AChE (Acetylcholinesterase) was downloaded from the RCSB-PDB website (PDB ID for AChE structure: 4M0E). The structure has a resolution of 2.00 Å and consists of 542 amino acid residues, without any mutations. Before conducting docking studies, the AChE enzyme protein structure underwent a thorough cleaning process using AutoDockTools 4.2 [ 28 ]. This involved the removal of all crystallographic water molecules, ligands, and any other crystallizing agents that might interfere with the docking simulation. Subsequently, polar hydrogens were added to the protein structure to ensure proper hydrogen-bond interactions during docking. Then, Kollman and Gasteiger charges were computed by AutoDock software to assign atom charges and showcase the electrostatic effects of the enzyme. The atomic types were then defined as AutoDock4 (AD4) types, ensuring compatibility with the AutoDock docking algorithm [ 29 ]. 2.3 Molecular Docking of Organophosphates with AChE molecules The optimized compound-protein complex of OPs-AChE was taken as a model to perform the rigid molecular docking analysis. The docking simulations were carried out using the tool AutoDock 4.2, which employed features like calculation of Genetic Algorithm on the simulation approach basis [ 28 ]. All other docking parameters were kept by default for the maintainance and standardization of the experiment. The output files were made using the Lamarckian Genetic Algorithm (LGA) method, which combines the genetic algorithm's global search capabilities with local optimization strategies for higher accuracy in docking predictions. Then the selection of top ten conformations for the enzyme-ligand complexes was done based on their most favorable negative binding energies (ΔG) and low RMSD values (Root Mean Square Deviation), indicating strong binding affinities and stability of the docked conformations [ 30 ],[ 31 ]. Post-docking analysis was performed using PyMOL and Discovery Studio software. These tools were basically used to visualize and study the molecular interactions between OPs and AChE, as well as to analyze binding energies, interaction sites, and conformational changes in the complexes [ 32 ]. 3. Results and Discussion 3.1 Computational experimentation for molecular modeling and docking on Organohosphate-AChE Complex Analysis of configuration of the OP compound Tricresyl phosphate in ground state was done through Gaussian 9 software, where we got information regarding the bond length and angle, along with the dihedral angles for each atom in the compound. For the rest of the OP compounds, information regarding configuration, bond angles and dihedral angles with respective energy minimization parameters is provided through supplementary data for this paper. After optimisation, no difference was observed regarding the bond lengths but slight changes in the bond angles was observed in the molecular structure of the OP compound. 3.2 Docking of OP with Acetylcholinesterase (AChE) Computational approaches such as molecular docking were also utilized to get an insight for the interaction between all 23 OPs and AChE which might not be possible to determine only by experimentation. Table 1 shows the docking score wise enlistment of 23 OPs after their interaction with AChE. For the RMSD value, best binding energy score of -5.45 Kcal/mol for the OP Tricresyl phosphate was observed at running loop of 7 at first rank, with reference RMSD of value 36.26 for the Tricresyl phosphate-AChE complex. Table 2 shows the compilation of RMSD values for all 23 OPs. Table 1 Docking scores of OPs and AChE interaction Organophosphates Docking score against AChE (kcal/mol) Tricresyl Phosphate -5.45 Tetrachlorvinphos -5.22 Azinphos-methyl -4.79 Chlorpyrifos -4.70 Azamethiphos -4.44 Diazinon -4.36 Sarin -4.15 Echothiophate -3.92 Soman -3.80 VX -3.79 Phosmet -3.67 Ethoprophos -3.65 Fenitrothion -3.61 Parathion -3.61 Dichlorvos -3.59 Disulfoton -3.53 Tabun -3.47 Isoflurophate -3.47 Methyl-parathion -3.38 Tribufos -3.19 Trichlorfon -3.17 Malathion -2.56 Ethion -1.89 Table 2 RMSD values obtained for all 23 OPs docking results. OPs Rank Run Binding Energy score RMSD (cluster) RMSD (reference) Tricresyl Phosphate 1 7 -5.45 0 36.26 Tetrachlorvinphos 1 9 -5.22 0 54.95 Azinphos-methyl 1 5 -4.79 0 55.8 Chlorpyrifos 1 6 -4.70 0 54.93 Azamethiphos 1 1 -4.44 0 54.61 Diazinon 1 10 -4.36 0 53.76 Soman 1 2 -4.15 0 41.44 Echothiophate 1 3 -3.92 0 54.06 Sarin 1 10 -3.80 0 53.18 VX 1 5 -3.79 0 52.76 Phosmet 1 4 -3.67 0 37.97 Ethoprophos 1 10 -3.65 0 54.76 Fenitrothion 1 5 -3.61 0 69.37 Parathion 1 3 -3.61 0 39.17 Dichlorvos 1 5 -3.59 0 53.98 Disulfoton 1 1 -3.53 0 52.92 Tabun 1 4 -3.47 0 51.06 Isoflurophate 1 8 -3.47 0 65.92 Methyl-parathion 1 6 -3.38 0 59.67 Tribufos 1 9 -3.19 0 54.28 Trichlorfon 1 1 -3.17 0 53.94 Malathion 1 1 -2.56 0 54.66 Ethion 1 8 -1.89 0 51.32 Figure 1 parts (a) and (b) show the docked structure of the OP compound Tricresyl phosphate with AChE made using PyMol and Discovery Studio software, where some amino acid residues of the protein show non-covalent interaction with the compound Tricresyl phosphate, demonstrating its binding at the enzyme's active site. In the van der Waals interaction, amino acids ILE 142, ARG 147, PRO 118 and MET 123 are involved; for pi-anion bonding, GLU 141 is involved; for pi-pi T-shaped bonding at one of the benzene rings, TYR 161 is involved; while LEU 182, TYR 138, ARG 186, PHE 134 and ALA 126 are involved in alkyl interaction. Both LEU 115 and LYS 137 are involved in pi-alkyl interaction. These interactions are summarised in Table 3 . Table 3 Table showing amino acids involved in non-covalent interactions between Tricresyl phosphate and AChE. Non-covalent interaction Amino Acid residue involved van der Waals ILE 142, ARG 147, PRO 118, MET 123 Pi-anion GLU 141 Pi-Pi T-shaped TYR 161 Alkyl interaction LEU 182, TYR 138, ARG 186, PHE 134, ALA 126 Pi-alkyl LEU 115, LYS 137 The above results show that OP compound Tricresyl phosphate has good binding affinity with Acetylcholinesterase, showing it to be a promising candidate for further study in OP toxicity with regard to AChE. Conclusion To understand how OP toxicity influences human neurological processes and cause the related diseases, the biological mechanism of organophosphates (OP) interacting with their prime target acetylcholinesterase (AChE) enzyme was needed to study, and analyse interactions of different OP compounds with the enzyme through in-silico methods. The modulation of chemical structures for the 23 OPs selected for this study showed how through changes in bond angle and length of the structures, energy minimization and gradient normalization can be affected to get optimal results. The outcome from molecular docking had shown a possibly good binding affinity among the OPs, with best results coming out for Tricresyl Phosphate (docking score of -5.45 Kcal/mol) and the least likely result for Ethion (-1.89 Kcal/mol). After visualisation through PyMol and DS, the OP-AChE complex was further analysed through LigPlot software to get a 2D visualisation of the complex stabilized mostly by hydrophobic interactions. All these observations can be further helpful in counteracting the efficacy of OPs when binding with synaptic enzymes like AChE, and their effects can be neutralized at early stage by developing potential antidotes, not just against the pesticides and nerve agents, but also for the OP chemicals whose interaction with human biological components at molecular level have been least researched. In summary, this study helps provide an insight about organophosphates and their toxic effects in the human body, and how through in-silico analysis such molecules can be targeted for reducing their binding affinity to biological compounds to at least prevent pathological and long-term diseases. Declarations Author Contributions TS performed the experiment, analysis, graphical designing and wrote the manuscript. AKV led the development of methodology for the experiment, data extraction, study quality assessment, conceptualization, study identification, analysis, manuscript writing and editing, and overall supervision. TS edited the whole draft and did the referencing. AKV helped in experiment and provided detailed reviews of the manuscript drafts and analysis, along with crucial feedback. Declaration of Interest The authors state that they have no known financial conflicts of interest or personal connections that could have influenced the work presented in this study. Acknowledgement The authors sincerely acknowledge all kinds of support from the School of Bioengineering and Biosciences, Lovely Professional University, Punjab, India. 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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-5622034","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":388910171,"identity":"7e5acd5d-a312-45f7-952f-6590c25b4292","order_by":0,"name":"Tanya Singh","email":"","orcid":"https://orcid.org/0000-0002-3817-145X","institution":"School of Bioengineering and Biosciences, Lovely Professional University, Punjab","correspondingAuthor":false,"prefix":"","firstName":"Tanya","middleName":"","lastName":"Singh","suffix":""},{"id":388910241,"identity":"a9bb19c5-a9b0-4fb8-a5a1-7a8a14b55df0","order_by":1,"name":"Awadhesh Kumar Verma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYDCCAwwMEmAGewOQMLAgRQvPAZAWCVK0SCSAScI6+G4ffnibp+JeNP/M51c3/CiQYOBv707Aq0XyXJqxNc+Z4twZt3PKbvYAHSZx5uwGvFoMzjCYSc5sS8htuJ2TdoMHqMVAIpeQFvZvkjP/JeTOv3km7eYf4rTwmEl8bEjI3XCD/dhtomyRPMNTbPHhWELuxjM5bLdlDCR4CPqF7wz7xhsJNQm5844ff3bzzR8bOf72XvxakACPAZgkVjkIsD8gRfUoGAWjYBSMIAAAzahMPORV/eoAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-1497-6210","institution":"School of Bioengineering and Biosciences, Lovely Professional University, Punjab","correspondingAuthor":true,"prefix":"","firstName":"Awadhesh","middleName":"Kumar","lastName":"Verma","suffix":""}],"badges":[],"createdAt":"2024-12-11 07:49:29","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5622034/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5622034/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71229116,"identity":"da76f202-edf0-4596-a7c0-4f321718399e","added_by":"auto","created_at":"2024-12-12 10:34:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":258376,"visible":true,"origin":"","legend":"\u003cp\u003e3D view of non-covalent interactions of OP-AChE complex; 1(b): 2D interactions of OP with AChE obtained through docking.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5622034/v1/fdc6356da43d5ba7fb3711ee.png"},{"id":71228672,"identity":"54185fe3-2837-49de-961e-b1c621d2eb1b","added_by":"auto","created_at":"2024-12-12 10:26:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":71147,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical plot for binding energy values of 23 OPs and their interaction with AChE.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5622034/v1/e992e7908b50a3c4b2639ad3.png"},{"id":71228685,"identity":"19cec59c-dbf1-465b-aa5d-ee6e5a63b179","added_by":"auto","created_at":"2024-12-12 10:26:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":168465,"visible":true,"origin":"","legend":"\u003cp\u003e(a): Snapshot showing the interaction between AChE and industrial chemical molecule Tricresyl Phosphate using LigPlot plus software. 3(b): Snapshot showing the interaction between AChE and pesticide molecule Ethion using LigPlot plus software.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5622034/v1/9e7a7982b18d079c5b2da9c9.png"},{"id":71229891,"identity":"bafeec4d-bb32-4ff0-9274-0130ef1db00b","added_by":"auto","created_at":"2024-12-12 10:42:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1097880,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5622034/v1/4219308c-3a41-424d-99d2-9d63a528166c.pdf"},{"id":71228680,"identity":"88f59b8e-2171-4607-9b65-4a4b474439c8","added_by":"auto","created_at":"2024-12-12 10:26:16","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":231462,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.png","url":"https://assets-eu.researchsquare.com/files/rs-5622034/v1/a7ce9781e3973dd99cbfce3d.png"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIn-silico\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e toxicity analysis for interaction between Organophosphates and Acetyl cholinesterase through molecular level simulation\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBeing the ester form of alcohol and phosphorus group and composed of varying organic compounds, organophosphates (OP) have exclusively been used in the manufacture and production of pesticides and insecticides, chemical agents for industrial applications and as nerve agents for biochemical hazard [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. They have lately emerged as potential toxicogenic components affecting the sustainability of humans and the environment of our earth. Initially, these were developed to target pests and insects responsible for harming crops, by affecting their nervous system through neurotoxic effects and causing long-term damage or death to the encroachers [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. But due to their excessive use in agricultural and industrial sectors, their effects are now being observed in the form of environmental pollution through biomagnification in aquatic food webs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], soil leaching causing groundwater pollution and harm to terrestrial life, and through air pollution which is directly or indirectly affecting the health of animals and human beings [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The condition of acute poisoning caused by OPs involve twitching of muscles, respiratory difficulties, seizures, insomnia, temporary dementia and confusion [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Chronic toxicity effects can have long-term impacts such as neurodegenerative disorders, bronchorrhea and lung paralysis, damage to liver, kidneys and other vital organs, certain carcinogenic effects and even death in fatal cases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Ongoing research is being conducted for pest control mechanisms to be less toxic, and implementation of strict rules and regulations for use of OPs for sustaining our living and our environment. Among humans, these compounds have been modified with fluoride and sulphur constituents to make nerve agents, for causing intentional harm for the purpose of chemical warfare or chemo-terrorism [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. They could be in odourless liquid form to be used as aerosol sprays, or are combined with other chemicals for increasing their shelf life for prolonged toxic use. More efforts are being made in formulating antidotes against these nerve agents, and for that context their chemical framework is needed to be understood, how these components are made to induce rapid action and high toxic effects along with maintaining their stable nature by design [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAcetylcholinesterase (AChE) is an important functional enzyme present in an organism's nervous system (the brain, the spinal cord, and neuro-muscular junctions) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], whose primary purpose is to break down acetylcholine (ACh), a neurotransmitter responsible for transmitting and ceasing nerve signals from synaptic gap of neurons to the motor nerves, and letting the muscles and nerve cells to relax and reset to combat spontaneous activation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. ACh tends to bind with the enzyme's activation region or site, which compels the neurotransmitter to act as catalyst in the process of hydrolyzation and convert into choline and acetate (Acetyl CoA). Such process is important for stimulation of brain activity and preventing muscle over-exhaustion at the same time [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The main target of OPs is to inhibit the working of AChE, where due to their interaction, ACh starts accumulating in the synapse gap, which deregulates the stimulation of motor nerve cells and muscles, causing a spontaneous cycle of hyper stimulation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This can cause muscle cramping, distress to neural and circulatory networks, contraction of muscles around the lungs causing distress and difficulty breathing, which in turn can lead to paralytic shock.\u003c/p\u003e \u003cp\u003eThrough the process of phosphorylation, the inhibition of AChE done by OPs help influence in their toxic effect. The first step involves \u003cb\u003ebinding\u003c/b\u003e, where the combination of OPs with AChE makes a covalent bond with serine (Ser) amino acid at the active site [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The second step involves \u003cb\u003einactivation of AChE\u003c/b\u003e, where the process of phosphorylation causes inactivation of the enzyme and prevents it from breaking down ACh [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In the third step, \u003cb\u003eACh accumulation\u003c/b\u003e in the synapse caused by inhibition of AChE causes rapid stimulation of synaptic receptors. Then, finally the process of \u003cb\u003eoverstimulation of nerve cells\u003c/b\u003e causes deregulation of nerve signals which leads to acute to chronic symptoms in the nervous system, further affecting the brain and other vital organs [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome vital studies have demonstrated the interaction of AChE and organophosphates, and how its inhibitory activity can be analysed at molecular level. One such study incorporated observations for interaction of OPs with AChE and Butyrylcholinesterase (BChE) where they demonstrated that the pesticide OP Ethoprophos showed more binding affinity property and had more inhibition towards AChE than BChE; and they also did the comparison of reactivators RS194B, 2-PAM and HI-6 for AChE, where the authors observed that RS194B had shown to be an effective reactivator for AChE [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Another study reviewed about the effects of OPs on different esterases where through a quantum mechanics molecular docking approach they studied the effects of aging on AChE by Sarin, Mipafox and Diisopropyl fluorophosphate (DFP), and they deduced that the complex of AChE with Mipafox had the highest energy barrier for aging process [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In a clinical case study, the authors tried to analyze tolerance level of enteral nutrition among OP poisoned patients who were on mechanical ventilation while being administered atropine, which is considered the main antidote for OP toxicity. They concluded that nutritional support is needed as part of toxicity removal and comprehensive therapy and can be integrated further in rehabilitation of patients suffering from effects of OP poisoning [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur objective would be to focus on giving a comparative analysis on the interactions of different components of Organophosphates with AChE at molecular level and whether their interactions would differ from each other respectively in terms of bonding and interaction with the binding site, along with emphasis on harmful effects of these components on human health [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]-[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Theoretical modeling and Optimization of Organophosphates as Ligand molecules\u003c/h2\u003e \u003cp\u003eThe three-dimensional (3D) theoretical modeling of 23 types of Organophosphates (Pesticides: \u003cem\u003eAzamethiphos, Azinphos-methyl, Chlorpyrifos, Diazinon, Dichlorvos, Ethion, Fenitrothion, Malathion, Parathion, Methyl-parathion, Phosmet, Tetrachlorvinphos;\u003c/em\u003e Nerve agents: \u003cem\u003eSarin, Soman, Tabun, VX;\u003c/em\u003e Industrial/Medical chemicals: \u003cem\u003eDisulfoton, Echothiophate, Ethoprophos, Isoflurophate, Tribufos, Trichlorfon and Tricresyl phosphate\u003c/em\u003e) was conducted using the Marvin Sketch software [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The molecular structures were initially refined in both two-dimensional (2D) and 3D forms. Following this, structural validation was performed using Marvin View to ensure accurate 3D conformational integrity. Subsequently, the geometries of the organophosphate molecules were optimized to their respective transition states, with energy minimization carried out in multiple stages. Intermediate energy minimizations were executed utilizing ChemDraw and Chem3DPro software, ensuring a progressive refinement of the molecular geometries [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e],[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor the feature DFT (Density Functional Theory), the Gaussian 09 package was used to obtain the eventual optimization for the molecules. The DFT calculations employed the RB3LYP functional in combination with the 6-311G basis set, offering a high level of computational accuracy for electronic structure calculations [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e],[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The optimized molecular geometries were later tried for molecular docking analysis to investigate respective interactions between the organophosphate compounds and acetylcholinesterase (AChE), a key enzyme for acetylcholine transport from neurons to muscles for inducing contraction and relaxation [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The docking analysis provided insights into the binding affinities and interaction patterns between the ligands and AChE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003e2.2 Preparation of AChE as Receptor molecule\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eThe three-dimensional structure for AChE (Acetylcholinesterase) was downloaded from the RCSB-PDB website (PDB ID for AChE structure: 4M0E). The structure has a resolution of 2.00 \u0026Aring; and consists of 542 amino acid residues, without any mutations. Before conducting docking studies, the AChE enzyme protein structure underwent a thorough cleaning process using AutoDockTools 4.2 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. This involved the removal of all crystallographic water molecules, ligands, and any other crystallizing agents that might interfere with the docking simulation. Subsequently, polar hydrogens were added to the protein structure to ensure proper hydrogen-bond interactions during docking. Then, Kollman and Gasteiger charges were computed by AutoDock software to assign atom charges and showcase the electrostatic effects of the enzyme. The atomic types were then defined as AutoDock4 (AD4) types, ensuring compatibility with the AutoDock docking algorithm [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Molecular Docking of Organophosphates with AChE molecules\u003c/h2\u003e \u003cp\u003eThe optimized compound-protein complex of OPs-AChE was taken as a model to perform the rigid molecular docking analysis. The docking simulations were carried out using the tool AutoDock 4.2, which employed features like calculation of Genetic Algorithm on the simulation approach basis [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. All other docking parameters were kept by default for the maintainance and standardization of the experiment. The output files were made using the Lamarckian Genetic Algorithm (LGA) method, which combines the genetic algorithm's global search capabilities with local optimization strategies for higher accuracy in docking predictions. Then the selection of top ten conformations for the enzyme-ligand complexes was done based on their most favorable negative binding energies (ΔG) and low RMSD values (Root Mean Square Deviation), indicating strong binding affinities and stability of the docked conformations [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e],[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Post-docking analysis was performed using PyMOL and Discovery Studio software. These tools were basically used to visualize and study the molecular interactions between OPs and AChE, as well as to analyze binding energies, interaction sites, and conformational changes in the complexes [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 Computational experimentation for molecular modeling and docking on Organohosphate-AChE Complex\u003c/h2\u003e\n \u003cp\u003eAnalysis of configuration of the OP compound Tricresyl phosphate in ground state was done through Gaussian 9 software, where we got information regarding the bond length and angle, along with the dihedral angles for each atom in the compound. For the rest of the OP compounds, information regarding configuration, bond angles and dihedral angles with respective energy minimization parameters is provided through supplementary data for this paper. After optimisation, no difference was observed regarding the bond lengths but slight changes in the bond angles was observed in the molecular structure of the OP compound.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Docking of OP with Acetylcholinesterase (AChE)\u003c/h2\u003e\n \u003cp\u003eComputational approaches such as molecular docking were also utilized to get an insight for the interaction between all 23 OPs and AChE which might not be possible to determine only by experimentation. Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the docking score wise enlistment of 23 OPs after their interaction with AChE. For the RMSD value, best binding energy score of -5.45 Kcal/mol for the OP Tricresyl phosphate was observed at running loop of 7 at first rank, with reference RMSD of value 36.26 for the Tricresyl phosphate-AChE complex. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e shows the compilation of RMSD values for all 23 OPs.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDocking scores of OPs and AChE interaction\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOrganophosphates\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDocking score against AChE (kcal/mol)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTricresyl Phosphate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e-5.45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTetrachlorvinphos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAzinphos-methyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChlorpyrifos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAzamethiphos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiazinon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEchothiophate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhosmet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEthoprophos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFenitrothion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParathion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDichlorvos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisulfoton\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTabun\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIsoflurophate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMethyl-parathion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTribufos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrichlorfon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalathion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEthion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e-1.89\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRMSD values obtained for all 23 OPs docking results.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOPs\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRun\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBinding Energy score\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRMSD (cluster)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRMSD (reference)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTricresyl Phosphate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-5.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTetrachlorvinphos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAzinphos-methyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChlorpyrifos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAzamethiphos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiazinon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEchothiophate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhosmet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEthoprophos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFenitrothion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e69.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParathion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDichlorvos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisulfoton\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTabun\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIsoflurophate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMethyl-parathion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTribufos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrichlorfon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalathion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEthion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e parts (a) and (b) show the docked structure of the OP compound Tricresyl phosphate with AChE made using PyMol and Discovery Studio software, where some amino acid residues of the protein show non-covalent interaction with the compound Tricresyl phosphate, demonstrating its binding at the enzyme\u0026apos;s active site. In the van der Waals interaction, amino acids ILE 142, ARG 147, PRO 118 and MET 123 are involved; for pi-anion bonding, GLU 141 is involved; for pi-pi T-shaped bonding at one of the benzene rings, TYR 161 is involved; while LEU 182, TYR 138, ARG 186, PHE 134 and ALA 126 are involved in alkyl interaction. Both LEU 115 and LYS 137 are involved in pi-alkyl interaction. These interactions are summarised in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTable showing amino acids involved in non-covalent interactions between Tricresyl phosphate and AChE.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-covalent interaction\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAmino Acid residue involved\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003evan der Waals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eILE 142, ARG 147, PRO 118, MET 123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePi-anion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGLU 141\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePi-Pi T-shaped\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTYR 161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlkyl interaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLEU 182, TYR 138, ARG 186, PHE 134, ALA 126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePi-alkyl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLEU 115, LYS 137\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe above results show that OP compound Tricresyl phosphate has good binding affinity with Acetylcholinesterase, showing it to be a promising candidate for further study in OP toxicity with regard to AChE.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo understand how OP toxicity influences human neurological processes and cause the related diseases, the biological mechanism of organophosphates (OP) interacting with their prime target acetylcholinesterase (AChE) enzyme was needed to study, and analyse interactions of different OP compounds with the enzyme through in-silico methods. The modulation of chemical structures for the 23 OPs selected for this study showed how through changes in bond angle and length of the structures, energy minimization and gradient normalization can be affected to get optimal results. The outcome from molecular docking had shown a possibly good binding affinity among the OPs, with best results coming out for Tricresyl Phosphate (docking score of -5.45 Kcal/mol) and the least likely result for Ethion \u0026nbsp; (-1.89 Kcal/mol). After visualisation through PyMol and DS, the OP-AChE complex was further analysed through LigPlot software to get a 2D visualisation of the complex stabilized mostly by hydrophobic interactions. All these observations can be further helpful in counteracting the efficacy of OPs when binding with synaptic enzymes like AChE, and their effects can be neutralized at early stage by developing potential antidotes, not just against the pesticides and nerve agents, but also for the OP chemicals whose interaction with human biological components at molecular level have been least researched. In summary, this study helps provide an insight about organophosphates and their toxic effects in the human body, and how through in-silico analysis such molecules can be targeted for reducing their binding affinity to biological compounds to at least prevent pathological and long-term diseases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTS performed the experiment, analysis, graphical designing and wrote the manuscript. AKV led the development of methodology for the experiment, data extraction, study quality assessment, conceptualization, study identification, analysis, manuscript writing and editing, and overall supervision. TS edited the whole draft and did the referencing. AKV helped in experiment and provided detailed reviews of the manuscript drafts and analysis, along with crucial feedback.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors state that they have no known financial conflicts of interest or personal connections that could have influenced the work presented in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors sincerely acknowledge all kinds of support from the School of Bioengineering and Biosciences, Lovely Professional University, Punjab, India. Also, the authors also extend their heartfelt thanks to SCFBio, Indian Institute of Technology, Delhi (IIT-Delhi), India for providing computational facilities to conduct our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was required for this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAdeyinka A, Muco E, Regina AC, et al. Organophosphates. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499860/\u003c/li\u003e\n\u003cli\u003eNeylon J, Fuller JN, van der Poel C, Church JE, Dworkin S. Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish. \u003cem\u003eJournal of Developmental Biology\u003c/em\u003e. 2022;10(4):49. doi:10.3390/jdb10040049\u003c/li\u003e\n\u003cli\u003eOre OT, Adeola AO, Bayode AA, Adedipe DT, Nomngongo PN. 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Structure-based drug-development study against fibroblast growth factor receptor 2: molecular docking and Molecular dynamics simulation approaches. \u003cem\u003eScientific Reports\u003c/em\u003e. 2024;14(1):19439. doi:10.1038/s41598-024-69850-1\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Lovely Professional University","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":"Organophosphates, Acetyl cholinesterase, Molecular Docking, Density Function Theory, Toxicity.","lastPublishedDoi":"10.21203/rs.3.rs-5622034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5622034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eOrganophosphates act as the chief constituents of pesticides and nerve agents, and their toxicological effects have caused harm not just to our environment but to human beings as well. Here, we have observed how interaction of Organophosphates (OPs) with the synaptic enzyme Acetylcholinesterase (AChE) can provide effective insights into studying the biological manifestation of OPs causing human ailments like neurodegenerative diseases. To further analyze how these OP components when bound with functional enzymes in the human body induce neurodegenerative disorders, we present an \u003cem\u003ein-silico\u003c/em\u003eanalysis of the toxicity of Organophosphates (OPs) by their interaction with Acetyl cholinesterase (AChE), the enzyme responsible for regulating neuronal signalling and transmission among muscles and motor nerves. Computational analysis was done using molecular docking and density functional theory (DFT) approaches, where molecular docking simulations helped determine the binding affinity evaluation, interaction sites, and conformations of AChE when docked with OPs. DFT estimations explored molecular mechanisms for OP toxicity, electronic properties and reactivity of OP compounds selectively. Through docking results, relatively strong binding affinities between OPs and AChE was observed which suggested OPs potential interference with the enzyme's function. The molecular dynamics simulations for their interaction provided important insights for the molecular basis of organophosphate toxicity, emphasizing the importance of their interaction with neuronal functioning enzymes. Such computational approach could provide a valuable framework for OP toxicology prediction, along with further analysis for in-vitro and in-vivo experiments.\u003c/p\u003e","manuscriptTitle":"In-silico toxicity analysis for interaction between Organophosphates and Acetyl cholinesterase through molecular level simulation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-12 10:26:11","doi":"10.21203/rs.3.rs-5622034/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":"bf75466b-ae24-498d-ac0f-445b7f6b7ac8","owner":[],"postedDate":"December 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":41448046,"name":"Bioinformatics"},{"id":41448047,"name":"Computational Biology"},{"id":41448048,"name":"Molecular Biology"},{"id":41448049,"name":"Toxicology"},{"id":41448050,"name":"Neurology"},{"id":41448051,"name":"Scientific Communication"}],"tags":[],"updatedAt":"2024-12-12T10:26:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-12 10:26:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5622034","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5622034","identity":"rs-5622034","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}