All-Atom Molecular Dynamics Simulations of Entire Virus Capsid Reveal the Role of Ion Distribution in Capsid’s Stability

Tarasova, Elvira; Farafonov, Vladimir; Khayat, Reza; Okimoto, Noriaki; Komatsu, Teruhisa; Taiji, Makoto; Nerukh, Dmitry

doi:10.1021/acs.jpclett.6b02759

Cited by 47 publications

(48 citation statements)

References 34 publications

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“…The results of the publication allowed to conclude that the correct assembly of the virus proceeds in the presence of RNA, while empty capsids are not formed. We have also observed this behaviour of capsid deformation for a different virus PCV2 [5] when the genome is absent inside the capsid. We have shown that such instability is caused by incorrect distribution of ions on the capsid's surfaces (inside and outside).…”

supporting

confidence: 61%

“…A set of such viruses of various sizes can serve as convenient models for tuning and validating MD simulations. Figure 1 Cross-cut through the all-atom model of PCV2 capsid without genome immersed in a simulation box filled with explicit water [5] This perspective is devoted to all-atom MD simulations of whole viruses or their complete capsids. Importantly, we consider only works on atomistic modelling, excluding (much more numerous) publications on coarse grained simulations of viruses.…”

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confidence: 99%

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All-Atom Molecular Dynamics Simulations of Whole Viruses

Tarasova

Nerukh

2018

J. Phys. Chem. Lett.

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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.

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confidence: 61%

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confidence: 99%

All-Atom Molecular Dynamics Simulations of Whole Viruses

Tarasova

Nerukh

2018

J. Phys. Chem. Lett.

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“…Both structures are stable in physiological environments and they have good agreement with experimental data. We have demonstrated in our previous paper [18] the small value of the RMSD for the structures compared to the Xray structure.…”

Section: Accepted Manuscriptmentioning

confidence: 83%

Complete virus capsid at all-atom resolution: Simulations using molecular dynamics and hybrid molecular dynamics/hydrodynamics methods reveal semipermeable membrane function

Tarasova

Korotkin

Farafonov

et al. 2017

Journal of Molecular Liquids

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“…The radial profile in the interior of the capsid is quite strong and likely to arise from the PCV2 N-terminus (amino acids 1-36) and additional material. We assumed that cellular RNA was present in the capsid to stabilize the positive charge of the capsid interior (66). To calculate the amount of RNA present in the PCV2 capsid, we used the asymmetric image reconstruction of MS2 (EMD-8397) as a standard -as the ssRNA genome of MS2 is resolved in this image reconstruction (22).…”

Section: Methodsmentioning

confidence: 99%

Structural characterization of the PCV2d genotype at 3.3 Å resolution reveals differences to PCV2a and PCV2b genotypes, a tetranucleotide, and an N-terminus near the icosahedral 3-fold axes

Khayat

Wen

Alimova

et al. 2019

Preprint

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17Porcine circovirus 2 (PCV2) is a T=1 non-enveloped icosahedral virus that has a major impact on the 18 swine industry as an agent of porcine circovirus associate disease. PCV2 capsid protein sequences 19 have been employed by others to provide a temporal description of the emerging genotypes. PCV2a 20 is believed to be the earliest genotype and responsible for giving rise to PCV2b, which gives rise to 21 PCV2d. The underlying mechanism responsible for the emerging genotypes is not understood. To 22 determine if a change in the PCV2d capsid accompanies the emergence of this genotype, we 23 determined the cryo-electron microscopy image reconstruction of PCV2d VLP at 3.3 Å resolution and 24 compared it to the previously reported PCV2a and PCV2b structures. Differences between the CD 25 and GH loops identify structural changes that accompany the emergence of PCV2b from PCV2a, and 26 PCV2d from PCV2b. We also model additional amino acids for the N-terminus near the icosahedral 27 3-fold axes of symmetry and a tetranucleotide between the 5-and 2-fold axes of symmetry. To 28 interpret the sequence diversity that defines the PCV2 genotypes on a structural platform we have 29 performed structure-based sequence comparison. Our analysis demonstrates that each genotype 30 possesses a unique set of amino acids located on the surface of the capsid that experience a high 31 degree of substitution. These substitutions may be a response to the PCV2 vaccination program. The 32 structural difference between PCV2a, b and d genotypes indicate that it is important to determine the 33 PCV2 capsid structure as the virus evolves into different genotypes. 34 35 3 Importance 36PCV2 is a significant epidemic agricultural pathogen that is the causative agent of a variety of swine 37 illnesses. PCV2 infections have significant economic impact in the swine industry and must be 38 controlled by vaccination. Outbreaks in farms vaccinated for PCV2 suggest that improvements to the 39 current vaccination programs are needed. Better understanding of the assembly, structure, replication 40 and evolution of these viruses is necessary for production of improved vaccines. The ability of PCV2 41 to rapidly shift genotypes suggests that expression systems capable of rapidly producing large 42 quantities of virus-like particles should be pursued. To these ends we have established a mammalian 43 cell-based virus-like particle expression system and performed high resolution structural studies of a 44 new PCV2 genotype. Differences between the structure of this genotype and earlier genotypes 45 demonstrate that it is important to study the PCV2 structure as it shifts genotypes. 46 47 Key Words: 48 Circovirus, virus-like particle (VLP), cryo-electron microscopy, virus evolution, capsid structure, 49 vaccine development 50 51 52Circoviruses are small nonenveloped icosahedral viruses that contain a circular, covalently 53 closed, single stranded DNA (ssDNA) genome. Circoviruses have been identified in a variety of 54 species and are known to cause infection...

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All-Atom Molecular Dynamics Simulations of Entire Virus Capsid Reveal the Role of Ion Distribution in Capsid’s Stability

Cited by 47 publications

References 34 publications

All-Atom Molecular Dynamics Simulations of Whole Viruses

All-Atom Molecular Dynamics Simulations of Whole Viruses

Complete virus capsid at all-atom resolution: Simulations using molecular dynamics and hybrid molecular dynamics/hydrodynamics methods reveal semipermeable membrane function

Structural characterization of the PCV2d genotype at 3.3 Å resolution reveals differences to PCV2a and PCV2b genotypes, a tetranucleotide, and an N-terminus near the icosahedral 3-fold axes

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