Homology Modeling and Molecular Dynamics Simulations of Transmembrane Domain Structure of Human Neuronal Nicotinic Acetylcholine Receptor

ABSTRACT

A three-dimensional model of the transmembrane domain of a neuronal-type nicotinic acetylcholine receptor (nAChR), (α4)^sub 2^(β2)^sub 3^, was constructed from a homology structure of the muscle-type nAChR recently determined by cryoelectron microscopy. The neuronal channel model was embedded in a fully hydrated DMPC lipid bilayer, and molecular-dynamics simulations were performed for 5 ns. A comparative analysis of the neuronal- versus muscle-type nAChR models revealed many conserved pore-lining residues, but an important difference was found near the periplasmic mouth of the pore. A flickering salt-bridge of α4-E266 with its adjacent β2-K260 was …