Two fundamental stages in influenza infection are viral attachment to the cell surface and membrane fusion to release the endocytosed viral contents. The influenza hemagglutinin protein is responsible for both these processes--binding of cell-surface glycans and membrane fusion. We wish to 1) predict what mutations to hemagglutinin are required for avian influenza to cross the species barrier and be transmitted readily between humans and 2) understand the physical means by which hemagglutinin perturbs cellular membranes to induce fusion. We study these molecular interactions by using physics-based simulation to parameterize statistical and mechanistic models, thus achieving a more robust physical understanding. These techniques for robust statistical interpretation of molecular simulation data enable computation to be employed in a systematic and quantitative fashion to achieve biological insight into influenza infection.

Peter M. Kasson, Nicholas W. Kelley, Nina Singhal, Marija Vrljic, Axel T. Brunger, and Vijay S. Pande. Ensemble molecular dynamics yields sub-millisecond kinetics and intermediates of membrane fusion. Proceedings of the National Academy of Sciences. 2006 Aug 8;103(32):11916-21.

Peter M. Kasson and Vijay S. Pande. Control of membrane fusion mechanism by lipid composition: predictions from ensemble molecular dynamics. PLOS Computational Biology, 2007 3(11): e220.

Peter M. Kasson and Vijay S. Pande. Structural basis for influence of viral glycans on ligand binding by influenza hemagglutinin. Biophys J. 2008 Oct;95(7):L48-50.

Peter M. Kasson and Vijay S. Pande. Combining sequence and structural information to assess influenza host-specificity mutants. Pacific Symposium on Biocomputing, 2009 in press.