Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding

A computational scanning mutagenesis method that combines the molecular mechanical and continuum solvent approaches and allows one to identify the `hotspots' in binding interfaces from a single trajectory of a wild type complex is developed.

Abstract

Significant progress has been achieved in computational methods to treat solvent effects in recent years. Among various techniques, the continuum solvent approach appears to be practically promising because it can be used to calculate reliable interaction and solvation energies in complex systems. A computational scanning mutagenesis method, one of such new approaches, has been recently developed. It combines the molecular mechanical and continuum solvent approaches and allows one to identify the `hotspots' in binding interfaces from a single trajectory of a wild type complex. Such techniques can be also used as a tool to optimize the interacting species for the binding, or as a ranking procedure in high throughput screening.