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
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.
Keywords
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
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