Computational Modelling of GPCRs

G-protein coupled receptors (GPCRs) are important pharmaceutical targets that are estimated to be the target for between 30 and 50% of current pharmaceuticals.  Although the general features of ligand binding to GPCRs is relatively well understood, much remains to be discovered about the precise mechanism of action of the proteins and the pathways of ligand binding.  This project will use molecular dynamics simulation running on high-performance computers combined with advanced modelling methods, such as the use of Markov State models, to investigate the binding of drugs to GPCRs and the dynamic behaviour of the proteins themselves. The information obtained through these studies will advance our understanding of GPCR function and inform GPCR drug design.

Techniques Used:
Molecular Dynamics, High Performance Computing, Markov Models

1.Thomas, T.; Fang, Y.; Yuriev, E.; Chalmers, D. K. Ligand Binding Pathways of Clozapine and Haloperidol in the Dopamine D-2 and D-3 Receptors. J Chem Inf Model 2016, 56 (2), 308-321.
2.Thomas, T.; McLean, K. C.; McRobb, F. M.; Manallack, D. T.; Chalmers, D. K.; Yuriev, E. Homology Modeling of Human Muscarinic Acetylcholine Receptors. J Chem Inf Model 2014, 54, 243−253.
3.Pande, V. S.; Beauchamp, K.; Bowman, G. R. Everything you wanted to know about Markov State Models but were afraid to ask. Methods 2010, 52 (1), 99-105.