Inspecting the Mechanism of Fragment Hits Binding on SARS-CoV-2 Mpro by Using Supervised Molecular Dynamics (SuMD) Simulations.
ChemMedChem ; 16(13): 2075-2081, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1384144
ABSTRACTComputational 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.
Full text: Available Collection: International databases Database: MEDLINE Main subject: Protease Inhibitors / Viral Matrix Proteins / Molecular Dynamics Simulation / SARS-CoV-2 Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: ChemMedChem Journal subject: Pharmacology / Chemistry Year: 2021 Document Type: Article Affiliation country: CMDC.202100156