Modeling of protein-ligand binding

Dnr:

SNIC 2016/1-434

Type:

SNAC Medium

Principal Investigator:

Yaoquan Tu

Affiliation:

Kungliga Tekniska högskolan

Start Date:

2016-11-01

End Date:

2017-11-01

Primary Classification:

10402: Fysikalisk kemi

Webpage:

http://www.theochem.kth.se/people/tu/

Allocation

Abstract

A ligand binding to a protein can change the structure and functions of the protein and therefore affect the related biological processes. Protein-ligand binding occurs in many biological processes. The knowledge of protein-ligand binding is also essential in structure-based drug design. Although the structures of ligand-binding domains of many important proteins have been determined experimentally, our understanding of protein-ligand interactions is still limited. For example, the ligand-binding affinity, which is a measure of the strength of the protein-ligand interactions, is still hard to determine both experimentally and theoretically. In this project, we will use new modeling approaches, such as metadynamics, to the study of ligand-protein interactions, including ligand binding modes and binding affinities. As water molecules in the protein receptors play crucial roles in ligand-protein interactions, the roles of water molecules in ligand-protein interactions and in the design of new ligand molecules will also be studied. By applying new modeling methods to the studies of protein-ligand interaction, we aim to elucidate the mechanism of protein-ligand interactions at the atomistic level.