Present experimental methods do not have sufficient resolution to investigate all processes in virus particles at atomistic details. We report the results of molecular dynamics simulations and analyze the connection between the number of ions inside an empty capsid of PCV2 virus and its stability. We compare the crystallographic structures of the capsids with unresolved N-termini and without them in realistic conditions (room temperature and aqueous solution) and show that the structure is preserved. We find that the chloride ions play a key role in the stability of the capsid. A low number of chloride ions results in loss of the native icosahedral symmetry, while an optimal number of chloride ions create a neutralizing layer next to the positively charged inner surface of the capsid. Understanding the dependence of the capsid stability on the distribution of the ions will help clarify the details of the viral life cycle that is ultimately connected to the role of packaged viral genome inside the capsid.

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CRESS-DNA viruses encompass a significant portion of the biosphere’s virome. However, little is known about the structure of Rep responsible for initiating the RCR of CRESS-DNA viruses.

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.

Two-phase flow analogy as an effective boundary condition for modelling liquids at atomistic resolution, Journal of Computational Science http://dx.doi.org/10. 1016/j.jocs.2016.03.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HighlightsWe have recently suggested and implemented a new approach to the problem of computing liquids at multiple scales in space and time based on the two-phase hydrodynamics analogy. Instead of separating the system into parts using boundaries, in the current hybrid approach the liquid is described as a nominally two-phase system consisting of both particle and continuum at the same time and using the continuum part of the model as an effective opendomain boundary condition for atomistic simulations. For the current paper, the method has been extended to dynamically tracking the atomistic-resolution features of interest which can evolve in the flow. Simulations of two very different biomolecular systems have been performed using our hybrid method implemented in the framework of the popular open-source GROMACS software. For both examples, it has been shown that the hybrid model can preserve important properties of the molecular part of the system. For the problem of peptide diffusion in water, the method has allowed obtaining the value of diffusion coefficient which is very close to that one of the reference all-atom simulation. For the virus in water problem, the method has preserved the structure of the virus capsid despite a relatively thin layer of molecular water around the proteins constituting the capsid, and which is in contrast with the all-atom simulation with the standard periodic boundary conditions. 3 Abstract A hybrid Molecular Dynamics/ Fluctuating Hydrodynamics framework based on the analogy with two-phase hydrodynamics has been extended to dynamically tracking the feature of interest at all-atom resolution. In the model, the hydrodynamics description is used as an effective boundary condition to close the molecular dynamics solution without resorting to standard periodic boundary conditions. The approach is implemented in a popular Molecular Dynamics package GROMACS and results for two biomolecular systems are reported. A small peptide dialanine and a complete capsid of a virus porcine circovirus 2 in water are considered and shown to reproduce the structural and dynamic properties compared to those obtained in theory, purely atomistic simulations, and experiment.

We present the results of Molecular Dynamics simulations of a viral capsid with the aim to analyse ion distribution on the capsid's surface that defines its stability. Two systems were modelled, a stable capsid with neutralising number of ions and an unstable capsid with low number of ions. For the ion distribution analysis the capsid's structure was identical and fixed in both simulations. It was then released for the stability analysis. The ion distribution demonstrated two types of the local regions on the inner surface of the capsid's wall: highly occupied with chloride ions in both systems despite a largely uniform electrostatic potential everywhere on the surface, and the regions that loose almost all chloride ions in the unstable capsid. The latter regions are located close to the cracks that are formed when the capsid is destabilised and thus could initiate the collapse of the capsid.

Rolling circle replication (RCR) is ubiquitously used by cellular and viral systems for genome and plasmid replication. While the molecular mechanism of RCR has been described, the structural mechanism is desperately lacking. Circular-rep encoded single stranded DNA (CRESS-DNA) viruses employ a viral encoded replicase (Rep) to initiate RCR. The recently identified prokaryotic homologues of Reps may also be responsible for initiating RCR. Reps are composed of an endonuclease, oligomerization, and ATPase domain. Recent structural studies have provided structures for all these domains such that an overall mechanism of RCR initiation can begin to be synthesized. However, structures of Rep in complex with its various DNA substrates and/or ligands are lacking. Here we provide a 3D bioinformatic review of the current structural information available for Reps. We combine an excess of 1590 sequences with experimental and predicted structural data from 22 CRESS-DNA groups to identify similarities and differences between Reps that lead to potentially important functional sites. Experimental studies of these sites may shed light on how Reps execute their functions. Furthermore, we identify Rep-substrate or Rep-ligand structures that are urgently needed to better understand the structural mechanism of RCR.

Spatiotemporal regulation of viral capsid assembly ensures selection of the viral genome for encapsidation. The porcine circovirus 2 is the smallest autonomously replicating pathogenic virus, yet it remains unknown how...