1. Inspecting the Mechanism of Fragment Hits Binding on SARS-CoV-2 M pro by Using Supervised Molecular Dynamics (SuMD) Simulations.
- Author
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Bissaro M, Bolcato G, Pavan M, Bassani D, Sturlese M, and Moro S
- Subjects
- Binding Sites, COVID-19 pathology, COVID-19 virology, Databases, Protein, Humans, Ligands, Protease Inhibitors metabolism, Retrospective Studies, SARS-CoV-2 isolation & purification, Viral Matrix Proteins metabolism, Molecular Dynamics Simulation, Protease Inhibitors chemistry, SARS-CoV-2 metabolism, Viral Matrix Proteins chemistry
- Abstract
Computational approaches supporting the early characterization of fragment molecular recognition mechanism represent a valuable complement to more expansive and low-throughput experimental techniques. In this retrospective study, we have investigated the geometric accuracy with which high-throughput supervised molecular dynamics simulations (HT-SuMD) can anticipate the experimental bound state for a set of 23 fragments targeting the SARS-CoV-2 main protease. Despite the encouraging results herein reported, in line with those previously described for other MD-based posing approaches, a high number of incorrect binding modes still complicate HT-SuMD routine application. To overcome this limitation, fragment pose stability has been investigated and integrated as part of our in-silico pipeline, allowing us to prioritize only the more reliable predictions., (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
- Published
- 2021
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