Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

ABSTRACT: We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repur

SUBMITTER: Acharya A 

PROVIDER: S-EPMC7754786 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature