Alpha7 nicotinic acetylcholine receptor agonists: prediction of their binding affinity through a molecular mechanics Poisson-Boltzmann surface area approach.
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.
Grazioso
Giovanni
G
Istituto di Chimica Farmaceutica e Tossicologica "Pietro Pratesi", Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
Cavalli
Andrea
A
De Amici
Marco
M
Recanatini
Maurizio
M
De Micheli
Carlo
C
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
C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor