Professor and Associate Chair
University of Maryland
Department of Chemical and Biomolecular Engineering
Live broadcast available:
Molecular simulations have been widely used to probe various cellular functions. These require accurate mathematical descriptions on how molecules interact that has been one focus of research in my lab. However, in this talk I will focus on two topics that involve membrane-associated proteins. First, the membrane binding of the oxysterol binding protein homologue (Osh4) was studied with all-atom MD to probe how this protein might function as an intracellular lipid transport protein. Our results suggest a complex binding motif that is preferred with a single lipid membrane and that lipid exchange between membranes occurs at membrane contact sites that activate this protein. Our simulation work also suggest that proper lipid-protein interactions are key to describing peripheral binding of Osh4 to the membrane. A simple domain of Osh4 is then simulated that is an amphipathic lipid packing sensor (ALPS). All-atom MD and an enhanced sampling technique are used to probe the mechanism of membrane binding and its bound structure and compared to initial experimental work on binding thermodynamics. To facilitate lipid transport, Osh4 must simultaneously bind to two membranes, and we have modeled this protein-mediated membrane contact site toward providing insight into the initial mechanism for intracellular lipid transport. The second project focuses on one of my lab’s projects to better understand the complexity of the SARS-CoV-2 infection to evade cellular immune response. Prior studies have demonstrated that an accessory protein of SARS-CoV-2 (ORF7a) localizes to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). Furthermore, expression of ORF7a is correlated with virulence in vivo and has a direct association with host bone marrow stromal antigen 2 (BST-2) suppresses its anti-viral activity. However, specific, structural models of these heterooligomeric interfaces are not known, nor is the key protein-protein interface. We are using multi-scale modeling and collaborating with Dr. Bryan Berger’s experimental lab at the University of Virginia to probe ORF7a/BST-2 dimerization. Machine learning has been used to cluster our simulation data to probe important protein-protein interfaces that drive dimerization and how human variations in BST-2 might lead to more severe infection. Our future goal is to develop a SARS-CoV-2 therapeutic that inhibits ORF7a/BST-2 dimerization and function.
Professor Jeffery Klauda received a B.S. in Chemical Engineering and Applied Mathematics from Rensselaer Polytechnic Institute. His Ph.D. research was done at the University of Delaware under the advisement of Prof. Stanley Sandler focusing on thermodynamic modeling of gas hydrates and gas adsorption on nanoporous carbons. He switched his research focus to biological areas and molecular simulation during his postdoctoral fellowship at the National Institutes of Health under the advisement of Drs. Bernie Brooks and Rich Pastor. In 2007, he joined as a tenure-track professor in the Department of Chemical and Biomolecular Engineering at the University of Maryland – College Park. He was the recipient of the NSF CAREER award and is currently a Full Professor. He is the Associate Chair/Director of Graduate Studies in the Department of Chemical and Biomolecular Engineering and is also the co-Director of the Biophysics Program. Prof. Klauda has published 132 peer-reviewed journal articles with an h-index of 40.