Modeling multiple species of nicotine and deschloroepibatidine interacting with alpha4beta2 nicotinic acetylcholine receptor: from microscopic binding to phenomenological binding affinity.

ABSTRACT: A variety of molecular modeling, molecular docking, and first-principles electronic structure calculations were performed to study how the alpha4beta2 nicotinic acetylcholine receptor (nAChR) binds with different species of two typical agonists, (S)-(-)-nicotine and (R)-(-)-deschloroepibatidine, each of which is distinguished by different free bases and protonation states. On the basis of these results, predictions were made regarding the corresponding microscopic binding free energies. Hydrogen-bonding and cation-pi interactions between the receptor and the respective ligands were found to be the dominant factors differentiating the binding strengths of different microscopic binding species. The calculated results and analyses demonstrate that, for each agonist, all the species are interc

SUBMITTER: Huang X 

PROVIDER: S-EPMC3182463 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature