Large-Scale Virtual Screening Against the MET Kinase Domain Identifies a New Putative Inhibitor Type.

ABSTRACT: By using an ensemble-docking strategy, we undertook a large-scale virtual screening campaign in order to identify new putative hits against the MET kinase target. Following a large molecular dynamics sampling of its conformational space, a set of 45 conformers of the kinase was retained as docking targets to take into account the flexibility of the binding site moieties. Our screening funnel started from about 80,000 chemical compounds to be tested in silico for their potential affinities towards the kinase binding site. The top 100 molecules selected-thanks to the molecular docking results-were further analyzed for their interactions, and 25 of the most promising ligands were tested for their ability to inhibit MET activity in cells. F0514-4011 compound was the most efficient and impaired

SUBMITTER: Bresso E 

PROVIDER: S-EPMC7070486 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature