The neuronal alpha 4 beta 2 nicotinic acetylcholine receptor (nAChR) is one of the most widely expressed nAChR subtypes in the brain. Its subunits have high sequence identity (54 and 46% for alpha 4 and beta 2, respectively) with alpha and beta subunits in Torpedo nAChR. Using the known structure of the Torpedo nAChR as a template, the closed-channel structure of the alpha 4 beta 2 nAChR was constructed through homology modeling. Normal-mode analysis was performed on this closed structure and the resulting lowest frequency mode was applied to it for a "twist-to-open" motion, which increased the minimum pore radius from 2.7 to 3.4 angstrom and generated an open-channel model. Nicotine could bind to the predicted agonist binding sites in the open-channel model but not in the closed one. Both models were subsequently equilibrated in a ternary lipid mixture via extensive molecular dynamics (MD) simulations. Over the course of 11 ns MD simulations, the open channel remained open with filled water, but the closed channel showed a much lower water density at its hydrophobic gate comprised of residues alpha 4-V259 and alpha 4-L263 and their homologous residues in the beta 2 subunits. Brownian dynamics simulations of Na+ permeation through the open channel demonstrated a current-voltage relationship that was consistent with experimental data on the conducting state of alpha 4 beta 2 nAChR. Besides establishment of the well-equilibrated closed- and open-channel alpha 4 beta 2 structural models, the MD simulations on these models provided valuable insights into critical factors that potentially modulate channel gating. Rotation and tilting of TM2 helices led to changes in orientations of pore-lining residue side chains. Without concerted movement, the reorientation of one or two hydrophobic side chains could be enough for channel opening. The closed- and open-channel structures exhibited distinct patterns of electrostatic interactions at the interface of extracellular and transmembrane domains that might regulate the signal propagation of agonist binding to channel opening. A potential prominent role of the beta 2 subunit in channel gating was also elucidated in the study.