Comparative assessment of QM-based and MM-based models for prediction of protein–ligand binding affinity trends

Abstract

ligand complexes. By using molecular fragmentation, the MIM method allows for accelerated QM calculations. We demonstrate that for classes of structurally similar ligands bound to a common receptor, MIM provides excellent correlation to experiment, surpassing the more popular Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) and Molecular Mechanics Generalized Born Surface Area (MM/GBSA) methods. The MIM method offers a relatively simple, well-defined protocol by which binding trends can be ascertained at the QM level and is suggested as a promising option for lead optimization in structure-based drug design.

Topics & Concepts