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Alpha7 nicotinic acetylcholine receptor agonists: Prediction of their binding affinity through a molecular mechanics Poisson–Boltzmann surface area approach
Author(s) -
Grazioso Giovanni,
Cavalli Andrea,
De Amici Marco,
Recanatini Maurizio,
De Micheli Carlo
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21019
Subject(s) - molecular mechanics , molecular dynamics , chemistry , acetylcholine receptor , nicotinic agonist , nicotinic acetylcholine receptor , entropy (arrow of time) , acetylcholine , docking (animal) , conformational entropy , boltzmann constant , receptor , computational chemistry , thermodynamics , physics , biochemistry , molecule , pharmacology , biology , organic chemistry , medicine , nursing
A group of agonists for the α7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies of binding Δ G bind were calculated by applying the molecular mechanics Poisson–Boltzmann surface area (MM‐PBSA) approach. This method, based on molecular dynamics simulations of fully solvated protein–ligand complexes, allowed us to estimate the contribution of both polar and nonpolar terms as well as the entropy to the overall free energy of binding. The calculated results were in a good agreement with the experimentally determined Δ G bind values, thereby pointing to the MM‐PBSA protocol as a valuable computational tool for the rational design of specific agents targeting the neuronal α7 nAChR subtypes. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008