Assessment of Conformational State Transitions of Class B GPCRs Using Molecular Dynamics.

ABSTRACT: Class B G protein-coupled receptors (GPCRs) comprise a family of 15 peptide-binding members, which are crucial targets for endocrine, metabolic, and stress-related disorders. While their protein structures and dynamics remain largely unclear, computer modeling and simulations represent a promising means to help solve such puzzles. Herein, we present a basic introduction to the methodology of molecular dynamics (MD) simulations and two analytical methods to assess the conformational ensembles and transitions of Class B GPCRs, using our recent studies of the human pituitary adenylate cyclase activating polypeptide (PAC₁) receptor as an example. From long MD simulations, conformational ensembles with different roles in ligand binding and receptor activation are sampled to establish

SUBMITTER: Liao C 

PROVIDER: S-EPMC6571028 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature