High-resolution mining of the SARS-CoV-2 main protease conformational space: supercomputer-driven unsupervised adaptive sampling.

ABSTRACT: We provide an unsupervised adaptive sampling strategy capable of producing μs-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs). The global exploration problem is decomposed into a set of separate MD trajectories that can be restarted within a selective process to achieve sufficient phase-space sampling. Accurate statistical properties can be obtained through reweighting. Within this highly parallel setup, the Tinker-HP package can be powered by an arbitrary large number of GPUs on supercomputers, reducing exploration time from years to days. This approach is used to tackle the urgent modeling problem of the SARS-CoV-2 Main Protease (M^pro) producing more than 38 μs of all-atom simulations of its apo (ligand-free) di

SUBMITTER: Jaffrelot Inizan T 

PROVIDER: S-EPMC8179654 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature