Dr. Régis Pomès

Molecular Structure and Function, Hospital for Sick Children, and Department of Biochemistry, University of Toronto

Integral membrane proteins fulfill vital functions involving signalling, recognition, and the exchange of ions and nutrients. Thus, the rapid passage of cations in and out of excitable cells through selective pathways in specialized membrane proteins called ion channels underlies the generation and regulation of electrical signals in all living organisms. Accordingly, the malfunction of membrane proteins is linked to numerous diseases such as cystic fibrosis and membrane proteins are top targets of drug design efforts. Biological membranes are also the arena in which many battles of bacterial infection and immune response are played out, which may hold clues for the design of new antibiotics. Finally, the interaction of amyloid-forming peptide oligomers with membranes is thought to play a role in the neurotoxicity of severe degenerative pathologies such as Alzheimer’s and Parkinson’s diseases.

Despite the importance of these processes to human health and disease, elucidating the molecular mechanisms underlying the interaction of peptides and proteins with lipid membranes has remained challenging. The combination of high-performance computing and efficient sampling algorithms makes it possible to access length- and time-scales relevant to the structure and function of peptides and proteins in lipid bilayers at the atomic level of detail. I will present recent and ongoing molecular simulation studies aimed at elucidating (1) the mechanism of ion transport and selectivity in voltage-gated sodium channels, (2) the interaction of antimicrobial peptides with lipid bilayers, and (3) the self-organization of amyloidogenic peptides at the membrane-water interface.

Dr. Régis Pomès is currently an associate professor at Department of Biochemistry at the University of Toronto. Dr. Pomès has received his PhD from University of Houston in 1993. His research in theoretical biophysics is related to understanding the basic physical principles that govern the fold and function of proteins as a way to predict and rationalize the biological activity of newly discovered proteins. His research group uses computer simulations to study biological systems at the molecular level. Three main directions of his research are:

• Studying the dynamic events involved in the folding and proper function of soluble proteins.

• developing novel computational methods for the prediction of protein-ligand binding affinities to help in the discovery of new therapeutic agents (rational drug design)

• studying the molecular mechanism of proton transport across biological membranes, a process which is essential to life itself (respiration, metabolism)