Paper Citing NAMD - Abstract
Saladino, A.C.; Xu, Y.; Tang, P.
Homology Modeling and molecular dynamics simulations of transmembrane domain structure of human neuronal nicotinic acetylcholine receptor
BIOPHYSICAL JOURNAL, 88:1009-1017, FEB 2005
A three-dimensional model of the transmembrane domain of a neuronal-type nicotinic acetylcholine receptor (nAChR), (alpha4)(2)(beta2)(3), was constructed from a homology structure of the muscle-type nAChR recently determined by cryo-electron 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 alpha4-E266 with its adjacent beta2-K260 was observed in the neuronal-type channel during the course of the molecular-dynamics simulations. The narrowest region, with a pore radius of similar to2 Angstrom formed by the salt-bridges, does not seem to be the restriction site for a continuous water passage. Instead, two hydrophobic rings, formed by alpha4-V259, alpha4-L263, and the homologous residues in the beta(2)-subunits, act as the gates for water flow, even though the region has a slightly larger pore radius. The model offers new insight into the water transport across the (alpha4)(2)(beta2)(3) nAChR channel, and may lead to a better understanding of the structures, dynamics, and functions of this family of ion channels.
