Pathways and Mechanism of Caffeine Binding to Human Adenosine A_2A Receptor.

ABSTRACT: Caffeine (CFF) is a common antagonist to the four subtypes of adenosine G-protein-coupled receptors (GPCRs), which are critical drug targets for treating heart failure, cancer, and neurological diseases. However, the pathways and mechanism of CFF binding to the target receptors remain unclear. In this study, we have performed all-atom-enhanced sampling simulations using a robust Gaussian-accelerated molecular dynamics (GaMD) method to elucidate the binding mechanism of CFF to human adenosine A_2A receptor (A_2AAR). Multiple 500-1,000 ns GaMD simulations captured both binding and dissociation of CFF in the A_2AAR. The GaMD-predicted binding poses of CFF were highly consistent with the x-ray crystal conformations with a characteristic hydrogen bond formed betwee

SUBMITTER: Do HN 

PROVIDER: S-EPMC8111288 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature