Title
Free Energies of the Disassembly of Viral Capsids from a Multiscale Molecular Simulation Approach
Date Issued
24 February 2020
Access level
open access
Resource Type
journal article
Author(s)
Polish Academy of Sciences
Publisher(s)
American Chemical Society
Abstract
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.
Start page
974
End page
981
Volume
60
Issue
2
Language
English
OCDE Knowledge area
Virología
Ingeniería mecánica
Scopus EID
2-s2.0-85078681763
PubMed ID
Source
Journal of Chemical Information and Modeling
ISSN of the container
15499596
Sponsor(s)
The authors thank Matias Machado for providing us with initial configurations of the TrV capsids simulations and fruitful discussions regarding the SIRAH forcefield. In addition, the authors thank Torsten Stuehn, Tomasz Lipniacki and Simon Poblete for their feedback on the Manuscript. This research has been supported by the Slovenian Research Agency (Research Core Funding No. P1-0055); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project Number 233630050, TRR 146; the National Science Centre, Poland, under Grant No. 2017/26/D/NZ1/00466, and by CONICYT (Chile) through FONDECYT Iniciación No. 11160768 and Basal FB0821. The authors also thank the computer resources from CCTVal and MPCDF from the Max Planck Society.
Sources of information:
Directorio de Producción Científica
Scopus