Molecular Modelling and Pharmacology of G protein-coupled Receptors

Many physiological processes are controlled through the activation of G protein-coupled receptors (GPCRs). 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. A recent breakthrough in structural biology disclosed the 3D structures of several GPCRs and provided opportunities to develop computational technologies for allosteric medicine discovery in GPCRs. 

In this PhD, you will study a GPCR using molecular dynamics simulations and cheminformatics approaches and predict novel allosteric binders. You then validate the developed protocols via mutagenesis and functional assays. 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 drug design research, which is applicable in academia and industry.