The intermolecular potential energy between a small organic molecule (a ligand) and a biological macromolecule is a key component of molecular docking and binding free energy calculations, which play an important role in computer-aided drug design. Ligand binding sites are typically near protein surfaces, where the local charge density can approach that of salt crystals! Although these charges can polarize the ligand electron density, this effect is not considered in the vast majority of molecular docking and binding free energy calculations. Moreover, there have been no large-scale studies evaluating the size of the embedding field of protein charges that needs to be considered, the magnitude of the polarization energy, and the impact that incorporating this energy has on binding affinity prediction. We address these questions based on QM/MM calculations for 286 protein-ligand complexes from the PDBBind Core Set.

Polarization effects on protein-ligand interaction energies

2019 Fall National Meeting

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