Recent advances in coarse-grained modeling of virus assembly

Hagan, Michael F.; Zandi, Roya

doi:10.1016/j.coviro.2016.02.012

Cited by 93 publications

(74 citation statements)

References 75 publications

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“…The application of ANM involves the diagonalization of a Hessian matrix of size 3N Â 3N, where N is the number of residues in the system. Due to the enormous size of viral particles, this calculation is not computationally feasible and only a select number of studies have explored the normal modes that describe the change between the conformations of a viral capsid (36,38,40,43). To reduce this expense, previous studies have exploited the symmetry of the virus capsid and defined the system as a set of rigid blocks under the rotation-translation of blocks method (44,45).…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Motions behind Enterovirus 71 Uncoating

Ross

Atılgan

Bishop

et al. 2018

Biophysical Journal

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Enterovirus 71 can be a severe pathogen in small children and immunocompromised adults. Virus uncoating is a critical step in the infection of the host cell; however, the mechanisms that control this process remain poorly understood. We applied normal mode analysis and perturbation response scanning to several complexes of the virus capsid and present a coarse-graining approach to analyze the full capsid. We show that our method offers an alternative to expressing the system as a set of rigid blocks and accounts for the interconnection between nodes within each subunit and protein interfaces across the capsid. In our coarse-grained approach, the modes associated with capsid expansion are captured in the first three nondegenerate modes and correspond to the changes observed in structural studies of the virus. We show that the resolution of the analysis may be modified without losing information on the global motions leading to uncoating. Perturbation response scanning revealed that a protomer cannot serve as a functional unit to explain deformations of the capsid. Instead, we define a pentamer as the minimum functional unit to investigate changes within the capsid. From the modal analysis and perturbation response scanning, we locate a hotspot region surrounding the fivefold axis. The range of the effect of these single, hotspot residues extend to 140 Å. The perturbation of internal capsid residues in this region displayed greatest propensity to capsid expansion, thus indicating the significant role that the RNA genome may play in triggering uncoating.

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Section: Introductionmentioning

confidence: 99%

Unraveling the Motions behind Enterovirus 71 Uncoating

Ross

Atılgan

Bishop

et al. 2018

Biophysical Journal

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“…Noteworthy, this modeling approach denotes a practical compromise given by the fact that all-atom simulations applied to the assembly of large macromolecular complexes such as viruslike aggregates are hardly feasible at present. 19 The viral genome has been treated as a flexible polymer or polyion chains with specific interactions, whereas the capsomer model, initially proposed by and later adopted by Mahalik and Muthukumar, 23 Zhang and Linse, 24,25 Zhang et al 26 Hagan and Zandi, 8 Perlmutter et al, 27 and Elrad and Hagan, 28 retained three prominent features for describing the virus formation. First, the coarse-grained building block representing a capsomer translates and rotates as a rigid body whose asymmetric shape is compatible with the icosahedral symmetry of the capsid, the choices being the triangular, [23][24][25][26]28 trapezoidal, [20][21][22] or pentagonal shape.…”

Section: Introductionmentioning

confidence: 99%

“…First, the coarse-grained building block representing a capsomer translates and rotates as a rigid body whose asymmetric shape is compatible with the icosahedral symmetry of the capsid, the choices being the triangular, [23][24][25][26]28 trapezoidal, [20][21][22] or pentagonal shape. 6,8,27,29 Second, the curvature allowing assembly toward the interior is obtained by designing truncated-pyramidal building block consisting of several layers of subunits. [23][24][25][26] Third, the required capsomer wedge in reaching the final icosahedral structure is obtained by enabling the right inclination angle of the lateral sides of the capsomer to the surface normal.…”

Section: Introductionmentioning

confidence: 99%

Assembled viral-like nanoparticles from elastic capsomers and polyion

Angelescu

2017

The Journal of Chemical Physics

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Molecular dynamics simulations are carried out on a coarse-grained model to describe the polyion driven co-assembly of elastic capsomers as viral-like aggregates. The kinetics and structural properties of the complexes are examined using cationic capsomers, an anionic polyion, both modelled using beads connected by springs, and counterions neutralizing separately the two charged species. Polyion overcharging the capsid is encapsulated owing to combined effects of the capsomer-capsomer short-range interactions, the polyion ability to follow a Hamiltonian path, and Donnan equilibrium. Conditions leading to a high yield of viral-like nanoparticles are found, and the simulations demonstrate that the capsomer elasticity provides mechanisms that improve the reliability toward correctly formed capsids. These mechanisms are related to a highly irregular capsomer cluster growth followed by the appearance of two stable capsomer clusters with the polyion acting as a tether between them. Elevated capsomeric flexibility provides an additional pathway to anneal the kinetically trapped structures by the ejection of a capsomeric monomer from a malformed complex followed by a rebinding step to form a correct capsid.

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“…Minimal coarse-grained molecular dynamics simulations have been widely used to investigate viral capsid formation as reviewed in Refs. [65,66], and to investigate the role of nucleic acids in virus assembly [7]. The capsid subunits, capsomeres, are typically described as a collection of beads that reproduces the overall shape of the subunit found in structural studies, as illustrated in Fig.…”

Section: Assembly Of Protein Microcompartmentsmentioning

confidence: 99%

Minimal coarse-grained models for molecular self-organisation in biology

Hafner

Krausser

Šarić

2019

Current Opinion in Structural Biology

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The molecular machinery of life is largely created via self-organisation of individual molecules into functional assemblies. Minimal coarse-grained models, where a whole macromolecule is represented by a small number of particles, can be of great value in identifying the main driving forces behind self-organisation in cell biology. Such models can incorporate data from both molecular and continuum scales, and their results can be directly compared to experiments. Here we review the state of the art of models for studying the formation and biological function of macromolecular assemblies in cells. We outline the key ingredients of each model and their main findings. We illustrate the contribution of this class of simulations to identifying the physical mechanisms behind life and diseases, and discuss their future developments. IntroductionSelf-assembly of individual molecules into large-scale functional structures generates the molecular machinery of life [1]. Such processes underlie the formation of cell membranes, protein filaments and networks, and drive the formation of three-dimensional genome structures. Many of these assemblies, such as protein filaments and lattices, also function as efficient nanomachines that enable cells to sense, move, divide, and transport materials in and out of the cell [2]. To sustain life, the formation of macromolecular assemblies needs to *

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Recent advances in coarse-grained modeling of virus assembly

Cited by 93 publications

References 75 publications

Unraveling the Motions behind Enterovirus 71 Uncoating

Unraveling the Motions behind Enterovirus 71 Uncoating

Assembled viral-like nanoparticles from elastic capsomers and polyion

Minimal coarse-grained models for molecular self-organisation in biology

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