Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity
In silico studies were performed to assess the binding affinity of selected organophosphorus compounds toward the acetylcholinesterase enzyme (AChE). Quantum mechanical calculations, molecular docking, and molecular dynamics (MD) with molecular mechanics Generalized–Born surface area (MM/GBSA) were...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/2/338 |
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| author | Rafal Madaj Bartłomiej Gostyński Arkadiusz Chworos Marek Cypryk |
| author_facet | Rafal Madaj Bartłomiej Gostyński Arkadiusz Chworos Marek Cypryk |
| author_sort | Rafal Madaj |
| collection | DOAJ |
| description | In silico studies were performed to assess the binding affinity of selected organophosphorus compounds toward the acetylcholinesterase enzyme (AChE). Quantum mechanical calculations, molecular docking, and molecular dynamics (MD) with molecular mechanics Generalized–Born surface area (MM/GBSA) were applied to assess quantitatively differences between the binding energies of acetylcholine (ACh; the natural agonist of AChE) and neurotoxic, synthetic correlatives (so-called “Novichoks”, and selected compounds from the G- and V-series). Several additional quantitative descriptors like root-mean-square fluctuation (RMSF) and the solvent accessible surface area (SASA) were briefly discussed to give—to the best of our knowledge—the first quantitative in silico description of AChE—Novichok non-covalent binding process and thus facilitate the search for an efficient and effective treatment for Novichok intoxication and in a broader sense—intoxication with other warfare nerve agents as well. |
| first_indexed | 2024-03-08T09:49:47Z |
| format | Article |
| id | doaj.art-857b90efc08243caba40679ef364867c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T09:49:47Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-857b90efc08243caba40679ef364867c2024-01-29T14:07:40ZengMDPI AGMolecules1420-30492024-01-0129233810.3390/molecules29020338Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding AffinityRafal Madaj0Bartłomiej Gostyński1Arkadiusz Chworos2Marek Cypryk3Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandIn silico studies were performed to assess the binding affinity of selected organophosphorus compounds toward the acetylcholinesterase enzyme (AChE). Quantum mechanical calculations, molecular docking, and molecular dynamics (MD) with molecular mechanics Generalized–Born surface area (MM/GBSA) were applied to assess quantitatively differences between the binding energies of acetylcholine (ACh; the natural agonist of AChE) and neurotoxic, synthetic correlatives (so-called “Novichoks”, and selected compounds from the G- and V-series). Several additional quantitative descriptors like root-mean-square fluctuation (RMSF) and the solvent accessible surface area (SASA) were briefly discussed to give—to the best of our knowledge—the first quantitative in silico description of AChE—Novichok non-covalent binding process and thus facilitate the search for an efficient and effective treatment for Novichok intoxication and in a broader sense—intoxication with other warfare nerve agents as well.https://www.mdpi.com/1420-3049/29/2/338NovichokAChEDFTbinding affinity |
| spellingShingle | Rafal Madaj Bartłomiej Gostyński Arkadiusz Chworos Marek Cypryk Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity Molecules Novichok AChE DFT binding affinity |
| title | Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity |
| title_full | Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity |
| title_fullStr | Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity |
| title_full_unstemmed | Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity |
| title_short | Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity |
| title_sort | novichok nerve agents as inhibitors of acetylcholinesterase in silico study of their non covalent binding affinity |
| topic | Novichok AChE DFT binding affinity |
| url | https://www.mdpi.com/1420-3049/29/2/338 |
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