Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations.

ABSTRACT: Acetylcholinesterase, with a deep, narrow active-site gorge, attracts enormous interest due to its particularly high catalytic efficiency and its inhibitors used for treatment of Alzheimer's disease. To facilitate the massive pass-through of the substrate and inhibitors, "breathing" motions to modulate the size of the gorge are an important prerequisite. However, the molecular mechanism that governs such motions is not well explored. Here, to systematically investigate intrinsic motions of the enzyme, we performed microsecond molecular dynamics simulations on the monomer and dimer of Torpedo californica acetylcholinesterase (TcAChE) as well as the complex of TcAChE bound with the drug E2020. It has been revealed that protein-ligand interactions and dimerization both keep the gorge in bulk,

SUBMITTER: Cheng S 

PROVIDER: S-EPMC5468367 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature