Conformation Transition of Intracellular Part of Glucagon Receptor in Complex With Agonist Glucagon by Conventional and Accelerated Molecular Dynamics Simulations.

ABSTRACT: The inactive conformations of glucagon receptor (GCGR) are widely reported by crystal structures that support the precision structure for drug discovery of type 2 diabetes. The previous study shows that the intracellular part is open in the glucagon-bound GCGR (glu-GCGR) and closed in the apo-GCGR by accelerated molecular dynamics (aMD) simulations. However, the crystal structure of GCGR in complex with partial agonist shows that the intracellular part is closed in the inactive conformation. To understand the differences between the studies of aMD simulations and crystal structure, the 2,500 ns conventional molecular dynamics (cMD) simulations are performed on the simulated model of glu-GCGR. The result shows that the transmembrane helices (TMH) 6 of glu-GCGR is outward ~4 Å to drive the i

SUBMITTER: Bai Q 

PROVIDER: S-EPMC6928006 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature