Unbinding ligands from SARS-CoV-2 Mpro via umbrella sampling simulations.

ABSTRACT: The umbrella sampling (US) simulation is demonstrated to be an efficient approach for determining the unbinding pathway and binding affinity to the SARS-CoV-2 Mpro of small molecule inhibitors. The accuracy of US is in the same range as the linear interaction energy (LIE) and fast pulling of ligand (FPL) methods. In detail, the correlation coefficient between US and experiments does not differ from FPL and is slightly smaller than LIE. The root mean square error of US simulations is smaller than that of LIE. Moreover, US is better than FPL and poorer than LIE in classifying SARS-CoV-2 Mpro inhibitors owing to the reciever operating characteristic-area under the curve analysis. Furthermore, the US simulations also provide detailed insights on unbinding pathways of ligands from the binding c

SUBMITTER: Tam NM 

PROVIDER: S-EPMC8790385 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature