Free Energies of the Disassembly of Viral Capsids from a Multiscale Molecular Simulation Approach

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 the description of
the entire viral capsid disassembly feasible. On the other hand, the
permanent development of novel molecular dynamics (MD) simulation
approaches, like enhanced 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.