Institute of Fundamental Technological Research

Molecular simulations 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 capsid disassembly. On the other hand, a permanent development of novel molecular dynamics (MD) simulation approaches like enhance sampling methods attempt to overcome the large time scales required for such simulations. Those methods have a potential for delivering molecular structures and properties of biological systems. Nonetheless, exploring the process on how a viral capsid disassembles by all-atom MD simulations has been rarely attempted. Here, we propose a methodology to analyze the disassembly process of viral capsids from a free energy perspective, through an efficient combination of dynamics using coarse-grained models and Poisson-Boltzmann simulations. 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 precalculated using CG simulations with the SIRAH force field. We used our multiscale approach on the Triatoma virus (TrV) as a test case, and find that even though an alkaline environment enhances the stability of the capsid, the resulting deprotonation of the genetic material generates a Coulomb-type electrostatic repulsion that triggers disassembly.