%0 Journal Article
%T Homology Model and Ligand Binding Interactions of the Extracellular Domain of the Human <i>¦Á</i>4<i>¦Â</i>2 Nicotinic Acetylcholine Receptor
%A Shu Mao
%A Hui Wen Ng
%A Michael Orr
%A Heng Luo
%A Hao Ye
%A Weigong Ge
%A Weida Tong
%A Huixiao Hong
%J Journal of Biomedical Science and Engineering
%P 41-100
%@ 1937-688X
%D 2016
%I Scientific Research Publishing
%R 10.4236/jbise.2016.91005
%X Addiction to nicotine, and possibly other tobacco constituents, is a major factor that contributes to the difficulties smokers face when attempting to quit smoking. Amongst the various subtypes of nicotinic acetylcholine receptors (nAChRs), the <i>¦Á</i>4<i>¦Â</i>2 subtype plays an important role in mediating the addiction process. The characterization of human <i>¦Á</i>4<i>¦Â</i>2-ligand binding interactions provides a molecular framework for understanding ligand-receptor interactions, rendering insights into mechanisms of nicotine addiction and may furnish a tool for efficiently identifying ligands that can bind the nicotine receptor. Therefore, we constructed a homology model of human <i>¦Á</i>4<i>¦Â</i>2 nAChR and performed molecular docking and molecular dynamics (MD) simulations to elucidate the potential human <i>¦Á</i>4<i>¦Â</i>2-ligand binding modes for eleven compounds known to bind to this receptor. Residues V96, L97 and F151 of the <i>¦Á</i>4 subunit and L111, F119 and F121 of the <i>¦Â</i>2 subunit were found to be involved in hydrophobic interactions while residues S153 and W154 of the ¦Á4 subunit were involved in the formation of hydrogen bonds between the receptor and respective ligands. The homology model and its eleven ligand-bound structures will be used to develop a virtual screening program for identifying tobacco constituents that are potentially addictive.
%K Nicotinic Acetylcholine Receptors
%K Homology Model
%K Ligand-Receptor Interactions
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=63168