WIDOCK: a reactive docking protocol for virtual screening of covalent inhibitors.

ABSTRACT: Here we present WIDOCK, a virtual screening protocol that supports the selection of diverse electrophiles as covalent inhibitors by incorporating ligand reactivity towards cysteine residues into AutoDock4. WIDOCK applies the reactive docking method (Backus et al. in Nature 534:570-574, 2016) and extends it into a virtual screening tool by introducing facile experimental or computational parametrization and a ligand focused evaluation scheme together with a retrospective and prospective validation against various therapeutically relevant targets. Parameters accounting for ligand reactivity are derived from experimental reaction kinetic data or alternatively from computed reaction barriers. The performance of this docking protocol was first evaluated by investigating compound series with div

SUBMITTER: Scarpino A 

PROVIDER: S-EPMC7904743 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature