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 α7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies of binding ΔGbind 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 ΔG 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.