Madaj, R.; Gostyński, B.; Chworos, A.; Cypryk, M. Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of their Non-Covalent Binding Affinity. Molecules2024, 29, 338.
Madaj, R.; Gostyński, B.; Chworos, A.; Cypryk, M. Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of their Non-Covalent Binding Affinity. Molecules 2024, 29, 338.
Madaj, R.; Gostyński, B.; Chworos, A.; Cypryk, M. Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of their Non-Covalent Binding Affinity. Molecules2024, 29, 338.
Madaj, R.; Gostyński, B.; Chworos, A.; Cypryk, M. Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of their Non-Covalent Binding Affinity. Molecules 2024, 29, 338.
Abstract
The in silico studies were performed in order to assess the binding affinity of selected organophosphorus compounds towards 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.
Keywords
Novichok; AChE; DFT; binding affinity
Subject
Chemistry and Materials Science, Organic Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
