Institute of Fundamental Technological Research

Molecular simulation of large biological systems, such as viral capsids, remains a challenging task in soft matter research. On one hand, coarse-grained (CG) models attempt to make feasible the description of the entire viral capsids. On the other hand, novel development of molecular dynamics (MD) simulation approaches, like enhance sampling which attempt to overcome the time scales required in biophysics. Those methods have a potential for delivering molecular structures and properties of biological systems. Nonetheless, exploring the process on how a capsid disassembles by all-atom MD simulations has been rarely attempted. Here, we propose a methodology to analyze the disassembly process of viral capsids quantitatively. In particular, we look at the effect of pH and charge of the genetic material inside the capsid, and compute the free energy of a disassembly trajectory by combining CG simulatiosn to a Poisson-Boltzmann solver. We employ such multiscale approach on the triatoma virus as a test case, and find that even though an alkaline environment enhances the stability of the capsid, the resulting deprotonation of the internal solvent generates an electrostatic repulsion that triggers disassembly.

Poisson Boltzmann, free energy, viral capsid, molecular dynamics, multiscale simulation, coarse graining, pH, protein assemblies