Understanding molecular recognition by kinetic network models constructed from molecular dynamics simulations.

Molecular recognition, the process by which biological macromolecules selectively bind, plays an important role in many biological processes. Molecular simulations hold great potential to reveal the chemical details of molecular recognition and to complement experiments. However, it is challenging to reconstruct the binding process for two-body systems like protein-ligand complexes because the system’s dynamics occurs on significantly different timescales due to several physical processes involved, such as diffusion, local interactions and conformational changes. In this chapter, we review some recent progress on applying Markov state models (MSMs) to twobody systems. Emphasis is placed on the value of projecting dynamics onto collective reaction coordinates and treating the ligand dynamics with different resolution models depending on the proximity of the protein and ligand. We also discuss some future directions on constructing MSMs to investigate molecular recognition processes.