Molecular dynamics of nicotinic acetylcholine receptor correlating biological functions.
The nicotinic acetylcholine receptor (nAChR) that mediates fast intercellular communication in response to neurotransmitters is a paradigm of ligand-gated ion channels. Molecular dynamics (MD) simulations are valuable in understanding membrane protein function at atomic level, providing useful clues for further experimental/theoretical studies. In this brief review, recent progress in MD simulations of the nAChR has been illustrated, mainly focusing on the latest simulation of the whole transmembrane domain of the receptor. On the basis of MD simulations, asymmetrical and asynchronous motions of five subunits were observed both in the ligand binding and transmembrane domains; a closed-to-open conformational shift of the gate was captured in different simulation systems; the contributions from the lipid molecules and other transmembrane segments rather than M2 to the gate switch as well as the conformational change of the whole channel were assessed; the dynamic behavior and related physical/chemical properties of the water molecules and cations within the ion channel were examined; and an experimentally comparable single-channel conductance and ion selectivity were obtained.
Xu
Yechun
Y
Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, and Graduate School, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Luo
Xiaomin
X
Shen
Jianhua
J
Zhu
Weiliang
W
Chen
Kaixian
K
Jiang
Hualiang
H
D007700:Kinetics; D008024:Ligands; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D011978:Receptors, Nicotinic