title: Alpha7 nicotinic acetylcholine receptor agonists: prediction of their binding affinity through a molecular mechanics Poisson-Boltzmann surface area approach.
abstract: A group of agonists for the alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies of binding DeltaG(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 DeltaG(bind) values, thereby pointing to the MM-PBSA protocol as a valuable computational tool for the rational design of specific agents targeting the neuronal alpha7 nAChR subtypes.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica "Pietro Pratesi", Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grazioso
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Marco
authors.initials: M
authors.lastname: De Amici
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
authors.forename: Carlo
authors.initials: C
authors.lastname: De Micheli
mesh_terms: D003198:Computer Simulation; D006801:Humans; D008956:Models, Chemical; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor