Microscopic binding of M5 muscarinic acetylcholine receptor with antagonists by homology modeling, molecular docking, and molecular dynamics simulation.

ABSTRACT: By performing homology modeling, molecular docking, and molecular dynamics (MD) simulations, we have developed three-dimensional (3D) structural models of the M5 muscarinic acetylcholine receptor (mAChR) and two complexes for M5 mAChR binding with antagonists SVT-40776 and solifenacin in the environment of lipid bilayer and solvent water. According to the simulated results, each of the antagonists is oriented horizontally in the binding pocket formed by transmembrane helices 2, 3, and 5-7. The cationic headgroup of each of the antagonists interacts with a negatively charged residue, Asp110, through electrostatic and hydrogen-bonding interactions. The simulated results also reveal some significant difference between the binding modes of SVT-40776 and solifenacin. In particular, SVT-40776 is

SUBMITTER: Huang X 

PROVIDER: S-EPMC3257414 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature