October 7, Tue 2014
1:00 pm, MRB 200
Dr. Olgun Guvench
Department of Pharmaceutical Sciences, University of New England College of Pharmacy
Using molecular simulation to understand protein:carbohydrate interactions involving the cell-surface receptor CD44
The cell-surface receptor CD44 is a single-pass transmembrane glycoprotein that can bind to hyaluronan (HA), which is a major carbohydrate component of extracellular matrix. Because of its role in helping the cell adhere to and communicate with the extracellular environment, CD44 has roles in normal tissue development and homeostasis, inflammation, and cancer. The CD44:HA binding interaction is known to be modulated both by conformational changes in the protein component of CD44 and by changes in the glycosylation state of CD44. Both of these processes involve significant biomolecular flexibility, making them difficult to study at an atomic resolution of detail using experimental approaches. We have therefore applied all-atom explicit-solvent molecular dynamics simulations to characterize these processes, thereby revealing how partial unfolding of the CD44 protein can increase HA binding affinity while specific glycosylation of the CD44 protein can inhibit HA binding.