The study of ligand-protein association process deepens our understanding of molecular recognition and binding kinetics. In this work, we applied all-atom molecular dynamics simulations with explicit solvent model to investigate kinetic mechanism of protein-ligand binding pathways. Through studying the case of HIVp and its neutral binders, we showed a series of binding intermediates. HIVp has two flexible loops called flaps that serve as a gate during the ligand binding processes. While a ligand approached, it induced conformational changes of flaps. Thus, the gate could show open conformation to help ligand access. Moreover, ligand may also likely bind to HIVp while the flaps are already with some changes. Ligand can quickly approached HIVp to form complex due to protein-ligand attraction, however, it took a lot of longer time for conformational arrangements to final stable bound structure. We hope this work can provide insights into ligand binding mechanism and further help design preferred-binding kinetics.

Molecular dynamics study of protein-ligand association pathway in case of HIV-1 protease

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.