Computer Simulations of G protein-coupled Receptors

Many physiological processes are controlled through the activation of G protein-coupled receptors (GPCRs) by regulatory peptides, making peptide GPCRs particularly useful targets for major human diseases such as diabetes and CNS diseases. It has become widely accepted that most GPCRs possess spatially distinct allosteric sites that can be targeted by small molecule ligands to modulate the receptor biological state. Allosteric binding sites offer advantages over orthosteric binding sites in identifying drugs with increased selectivity and structural novelty. However, the discovery of allosteric sites and modulators has been largely serendipitous, achieved through high-throughput screening. A recent breakthrough in structural biology disclosed the crystal structures of several GPCRs has provided opportunities to develop computational technologies for allosteric medicine discovery in GPCRs.
In this PhD, we will develop a computer methodology to map allosteric binding sites in GPCRs using molecular dynamics simulations and chemoinformtics approaches. You then validate the developed protocols via compound screening and mutagenesis. You will learn cutting-edge computational approaches in data collection, mining and analysis at the interface of chemistry and biology. The project facilitates skills development in the area of drug design research, which is applicable in academia and industry.