Hotspot Identification on Protein Surfaces Using Probe-Based MD Simulations: Successes and Challenges.

Molecular Dynamics (MD) based computational co-solvent mapping methods involve the generation of an ensemble of MD-sampled target protein conformations and using selected small molecule fragments to identify and characterize binding sites on the surface of a target protein. This approach incorporates atomic-level solvation effects and protein mobility. It has shown great promise in the identification of conventional competitive and allosteric binding sites. It is also currently emerging as a useful tool in the early stages of drug discovery. This review summarizes efforts as well as discusses some methodological advances and challenges in binding site identification process through these co-solvent mapping methods.