(597d) Exploring Virus Maturation Pathways Through Computer Simulations

During the maturation process of the bacteriophage HK97 the capsid swells to a larger size and also changes shape by becoming more faceted  (and less spherical).  The HK97 capsid consists of 420 protein subunits, the dimension of the capsid is ~50 nm and the time scale for maturation is on the order of hours; studying the maturation phenomenon from a molecular scale clearly necessitates a multiscale/enhanced sampling approach. As structures exist for both the immature and mature virus capsid, we have constructed structural pathways connecting the two end states.  This is done by constructing an initial “naive” pathway and then refining this pathway using a string method to evolve the pathway to a minimum energy pathway (MEP).  From the MEP we can compute the free energy profile and other physical properties. From in-vitro studies reducing the system pH enhances formation of the mature form and we will be examine how a low pH versus neutral pH environment will affect the thermodynamic and kinetic properties of the system.  Lastly, I will cover our attempts at understanding if icosahedral symmetry breaking occurs during maturation and if it facilitates formation of the mature state.  This is accomplished by employing coarse-grained simulations of the entire capsid with a potential energy function funneled toward the mature state.