Physical Sciences and Mathematics Commons^™

Rank-Ordering Protein-Ligand Binding Affinity By A Quantum Mechanics/ Molecular Mechanics/Poisson-Boltzmann-Surface Area Model, Mingliang Wang, Chung Wong

Chemistry & Biochemistry Faculty Works

The authors describe a quantum mechanics/molecular mechanics/Poisson-Boltzmann-surface area model for rank-ordering protein-ligand binding affinity in aqueous solution. Unlike many classical continuum electrostatics calculations in which the protein and ligand are treated as a uniform dielectric, this model uses quantum mechanics to explicitly describe the electronic polarization of the ligand by its environment. In solving the Poisson-Boltzmann equation, the authors use the quantum mechanical charge density directly rather than the common point-charge approximation. The authors show that useful results can be obtained by using experimental structure, by choosing a protein dielectric constant that is smaller than that typically used in classical …