Eric May (Theoretical and Computational Biophysics, University of Michigan, USA)
Abstract:In this talk, I will discuss multiscale computational approaches to understand the large- scale conformational and morphological changes, which viral capsids undergo as part of their viral life cycle. The primary motivation has been to understand the maturation process of the bacteriophage HK97, during which the virus transitions from a non- infectious spherical particle to an infectious particle with a faceted, polyhedral shape. We have approached this problem from both the mechanical (continuum elasticity) and thermodynamic (energy landscapes) viewpoints. I will discuss our theoretical and methodological advances in computing elastic properties of viral capsids from equilibrium fluctuations, and discuss the relationship between these calculations, experimental measurements and observed capsid shapes. I will also discuss our non- equilibrium studies addressing dynamical aspects of the HK97 maturation transition, including symmetry-breaking features and the underlying free-energy landscape governing these dynamics. By combining these viewpoints and employing a variety of simulation techniques at different resolution levels, one can begin to obtain a thorough understanding of viral processes, which otherwise would not be accessible through straight-forward simulation methods.