Rank-ordering protein-ligand binding affinity by a quantum mechanics/molecular mechanics/Poisson-Boltzmann-surface area model

Mingliang Wang; Wong, Chung F.
January 2007
Journal of Chemical Physics;1/14/2007, Vol. 126 Issue 2, p026101
Academic Journal
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 electrostatics calculations, and by performing the calculations in a manner that can improve the odds of cancellation of errors.


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