Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Thursday Speaker Abstracts

MEMBRANE REMODELING BY PROTEINS: INSIGHTS AND SURPRISES FROM MULTISCALE COMPUTER SIMULATION Gregory A Voth 1 ; 1 University of Chicago, Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, Chicago, IL, USA The protein-driven remodeling of biological membranes spans from the molecular to mesoscopic length and time scales. To access the full range of such complex processes, we employ a multiscale theoretical and computational methodology. The advantage of our approach is that it systematically connects all-atom molecular dynamics, coarse-grained (CG) modeling, and mesoscopic phenomena. We especially develop and apply methods for deriving CG models from protein structures and their underlying atomic-scale interactions, yielding accurate CG molecular dynamics (MD) simulation force fields. As a result, we can simulate large-scale biological process using information from the molecular level, which are inaccessible by standard atomistic MD simulation techniques. With this approach, we then can carefully study membrane remodeling mediated by various proteins. For example, with large scale CG molecular dynamics simulations, we investigate the way proteins interact with one another on the membrane and the underlying physics driving their assembly and generation of membrane curvature. A critical component of our multiscale approach is also its connection to experimental data, such as cryo- EM, cryo-ET, fluorescence, and optical tweezers. As time allows, specific applications of this simulation approach will be given for membrane remodeling by BAR domain proteins, HIV-1 virion budding and scission, and lipid droplet biogenesis. PROTEIN ACTIVATION AND MEMBRANE DEFORMATION IN ENVELOPED VIRUS ENTRY Peter Kasson 1,2 ; 1 University of Virginia, Departments of Molecular Physiology and Biological Physics, Charlottesville, VA, USA 2 Uppsala University, Department of Cell and Molecular Biology, Uppsala, Sweden Enveloped viruses infect cells via a process of membrane fusion between the viral membrane and a cellular membrane, mediated by viral fusion proteins. In many cases, the fusion proteins also perform receptor-binding functions, guiding the virus to particular cellular membranes where the protein is activated for fusion and entry occurs. We utilize a biophysical toolbox to dissect the requirements for fusion protein activation, the protein-membrane interactions involved in fusion, and the host membrane requirements for viral entry. I will present recent results from our group in these areas: how receptor binding affects the conformational equilibria controlling fusion protein activation and how host membrane deformability is a critical parameter controlling viral entry.

44