Computational Study of Conformational Changes in Nuclear Receptors Upon Ligand Binding

Abstract

The nuclear receptor superfamily (NR), as a major group of intracellular receptors, regulate broad aspects of cell functions. The activation of these receptors is regulated by endogenous or exogenous lipophilic compounds and regulatory proteins. They share a highly similar structure, particularly, in ligand binding domains (LBD) and DNA binding domains (DBD). These features all reveal NRs remarkable role in organism survival and highlight them as promising targets for therapeutic development. Meanwhile, advancements in computer-aided drug discovery have facilitated the expensive conventional methods of drug discovery.

Leveraging the computational advancements in the drug discovery process, our research on NRs has led to four publications and one manuscript. In our projects, we employed microsecond-long all-atom molecular dynamics (MD) simulations with relevant systems to investigate the dynamic behaviour and conformational changes of NRs induced by ligand binding.