Comparative assessment of QM-based and MM-based models for prediction of protein–ligand binding affinity trends
Sarah Maier, Bishnu Thapa, Jon A. Erickson, Krishnan Raghavachari · Physical Chemistry Chemical Physics · 2022
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.