Coarse-Grained Simulations of the Assembly of Empty Viral Capsids

Abstract

The morphogenesis of a virus is one of the most important steps in its life cycle, since a well-formed structure is vital to survive in hostile environments and to infect hosts. Viral selfassembly resembles a nucleation process where individual proteins stochastically form aggregates driven by a favourable free-energy of binding. The kinetics of the process is strongly regulated by the existence of a free-energy barrier between the viral constituents in solution and the fully-formed virus, in analogy with a first-order phase transition. In this work a coarse-grained model of viral assembly units is implemented in a Brownian Dynamics simulation and used to characterize viral nucleation kinetics. From simulations we evaluate the steady-state rate of capsid formation and reconstruct the free-energy landscape of the process, from which the critical capsid size and the nucleation barrier are obtained. Finally, a brief comparison of the simulations results with the predictions of classical nucleation theory (CNT) is discussed