Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways.

ABSTRACT: G protein-coupled receptors (GPCRs) constitute a functionally diverse protein family and are targets for a broad spectrum of pharmaceuticals. Technological progress in X-ray crystallography and cryogenic electron microscopy has enabled extensive, high-resolution structural characterisation of GPCRs in different conformational states. However, as highly dynamic events underlie GPCR signalling, a complete understanding of GPCR functionality requires insights into their conformational dynamics. Here, we present a large dataset of molecular dynamics simulations covering 60% of currently available GPCR structures. Our analysis reveals extensive local "breathing" motions of the receptor on a nano- to microsecond timescale and provides access to numerous previously unexplored receptor conformatio

SUBMITTER: Aranda-Garcia D 

PROVIDER: S-EPMC11868581 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature