Computational exploration of protein ligand interaction and its applications in drug discovery

Abstract

My PhD research can be summarized as two major directions. One direction is the theoretical investigation of protein conformational dynamics. In particular, we have developed a new approach to perform quantitative characterization of the ligand binding mechanisms by integrating Markov State Models, molecular dynamics (MD) simulations and flux analysis. This approach makes it possible to elucidate atomic details of protein-ligand recognition, and thus holds great promise to be widely applied to study various biological processes. In addition, we have also elucidated the free energy landscape for the transporting mechanisms of an ATP-binding cassette transporter MalFGK2 by applying MD simulations and the metadynamics enhanced sampling algorithm. The other direction of my PhD research is focused on the computer aided drug discovery. We have identified a novel inhibitor for the EphA4 receptor which is associated with Alzheimer’s disease. This compound was discovered via virtual screening of an in-house traditional Chinese medicine compound library. Finally, using molecular docking and MD simulations, we have also revealed mechanisms for a series of natural compounds Thalassospiramides inhibiting calpain protein.

Date of Award	2015
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology