Hidden GPCR structural transitions addressed by multiple walker supervised molecular dynamics (mwSuMD).

ABSTRACT: The structural basis for the pharmacology of human G protein-coupled receptors (GPCRs), the most abundant membrane proteins and the target of about 35% of approved drugs, is still a matter of intense study. What makes GPCRs challenging to study is the inherent flexibility and the metastable nature of interaction with extra- and intracellular partners that drive their effects. Here, we present a molecular dynamics (MD) adaptive sampling algorithm, namely multiple walker supervised molecular dynamics (mwSuMD), to address complex structural transitions involving GPCRs without energy input. We first report the binding and unbinding of the vasopressin peptide from its receptor V₂. Successively, we present the complete transition of the glucagon-like peptide-1 receptor (GLP-1R) from i

SUBMITTER: Deganutti G 

PROVIDER: S-EPMC12043319 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature