Abstract

This study reports the comparative molecular modeling, docking and dynamic simulations of human a9a10 nicotinic acetylcholine receptors complexed with acetylcholine, nicotine and a-conotoxin RgIA, using as templates the crystal structures of Aplysia californica and Lymnaea stagnalis acetylcholine binding proteins. The molecular dynamics simulations showed that Arg112 in the complementary a10(-) subunit, is a determinant for recognition in the site that binds small ligands. However, Glu195 in the principal a9(+), and Asp114 in the complementary a10(-) subunit, might confer the potency and selectivity to a-conotoxin RgIA when interacting with Arg7 and Arg9 of this ligand. © 2008 Elsevier Ltd. All rights reserved.