Membrane-Mediated Ligand Unbinding of the PK-11195 Ligand from TSPO.

ABSTRACT: The translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is of longstanding medical interest as both a biomarker for neuroinjury and a potential drug target for neuroinflammation and other disorders. Recently, it was shown that ligand residence time is a key factor determining steroidogenic efficacy of TSPO-binding compounds. This spurs interest in simulations of (un)binding pathways of TSPO ligands, which could reveal the molecular interactions governing ligand residence time. In this study, we use a weighted ensemble algorithm to determine the unbinding pathway for different poses of PK-11195, a TSPO ligand used in neuroimaging. In contrast with previous studies, our results show that PK-11195 does not dissociate directly into the solvent but instead d

SUBMITTER: Dixon T 

PROVIDER: S-EPMC7820730 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature