All-Atom Molecular Dynamics Simulations of Whole Viruses

Abstract

Classical molecular dynamics modeling of whole viruses or their capsids in explicit water is discussed, and known examples from the literature are analyzed. Only works on all-atom modeling in explicit water are included. Physical chemistry of the whole system is the focus, which includes the structure and dynamics of the biomolecules as well as water and ion behavior in and around the virus particle. It was demonstrated that in most investigations molecular phenomena that currently can not be studied experimentally are successfully reproduced and explained by the simulations. These include, for example, transport and distribution of ions inside viruses that ultimately connected to their stability, the hydrodynamic pressure in the capsid related to viruses' elastic properties, the role of metal ions in virus swelling, and others. Current and future tendencies in the development of all-atom virus simulations are outlined.

MS2 bacteriophage capsid studied using all-atom molecular dynamics

“…For viruses, interaction with the aqueous solution is the only external force that defines the structure and dynamics, and modelling of water is well developed in MD. Despite the substantial computing resources needed for such simulation, the number of viruses simulated at all-atom resolution is growing (see the reviews on all known simulations up to date [4,5]).…”

Editorial: Multiscale Modeling From Macromolecules to Cell: Opportunities and Challenges of Biomolecular Simulations

“…Therefore, the history of molecular simulations is strongly interlaced with that of computing hardware development, both tracing back to the more than 50 years ago. The exponential increase of computing system performances up to now has led to the possibility of addressing whole viruses or (portion of) cells at the atomistic level in simulations of hundreds of ns (Tarasova and Nerukh, 2018), while simulations of single proteins can extend over the milliseconds scale (Shaw et al, 2009). However, at the moment fully atomistic MD simulations cannot access simultaneously macroscopic sizes and time scales large enough for a sufficient statistical exploration.…”

A Laboratory Model for Virus Particle Nanoindentation

“…design of artificial drug delivery vectors. In teasing out the structure-function relationship it is often required to experiment with and model the collective behavior of molecules that make a virus (21,35). However, the highly successful methods of structural molecular biology are more apt to interrogate molecular properties in atomic detail than collective phenomena.…”

“…For instance, looking at the atomic structure of a virus or artificial viruslike particle designed to operate as a delivery vector would provide little (if any) information on the stored mechanical stresses that might influence how the virus interacts with a cell membrane. Thus, the large number of atoms and temporal dynamic range relevant to virus assembly are challenging to theoretic methods with atomic precision (although tremendous progress has been made in the past decade) (35). Most efforts have relied on reduced models that retain those physical aspects, which are hypothesized to be essential.…”