Multiscale modelling and simulation of viruses.

In recent years, advances in structural biology, integrative modelling, and simulation approaches have allowed us to gain unprecedented insights into viral structure and dynamics. In this article we survey recent studies utilizing this wealth of structural information to build computational models of partial or complete viruses and to elucidate mechanisms of viral function. Additionally, the close interplay of viral pathogens with host factors - such as cellular and intracellular membranes, receptors, antibodies, and other host proteins - makes accurate models of viral interactions and dynamics essential. As viruses continue to pose severe challenges in prevention and treatment, enhancing our mechanistic understanding of viral infection is vital to enable the development of novel therapeutic strategies.

[1]  D. Reguera,et al.  Viral nanomechanics with a virtual atomic force microscope , 2018, Journal of physics. Condensed matter : an Institute of Physics journal.

[2]  A. Nomoto,et al.  All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution. , 2014, The Journal of chemical physics.

[3]  Niranjan Nagarajan,et al.  In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation. , 2016, Molecular cell.

[4]  Klaus Schulten,et al.  Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography , 2013, PLoS pathogens.

[5]  D. Angelescu.  Assembled viral-like nanoparticles from elastic capsomers and polyion. , 2017, The Journal of chemical physics.

[6]  C. San Martín,et al.  Role of Condensing Particles in Polymer Confinement: A Model for Virus-Packed "Minichromosomes". , 2017, Biophysical journal.

[7]  K. Schulten,et al.  Atomic Modeling of an Immature Retroviral Lattice Using Molecular Dynamics and Mutagenesis. , 2015, Structure.

[8]  Qiangfeng Cliff Zhang,et al.  Integrative Analysis of Zika Virus Genome RNA Structure Reveals Critical Determinants of Viral Infectivity. , 2018, Cell host & microbe.

[9]  Daniel M. Hinckley,et al.  A Molecular View of the Dynamics of dsDNA Packing Inside Viral Capsids in the Presence of Ions. , 2017, Biophysical journal.

[10]  Thorsten Wohland,et al.  Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations. , 2019, Structure.

[11]  Niranjan Nagarajan,et al.  Structure mapping of dengue and Zika viruses reveals functional long-range interactions , 2019, Nature Communications.

[12]  A. Engelman,et al.  CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction , 2017, Science Advances.

[13]  Antonio Caliri,et al.  Membrane vesiculation induced by proteins of the dengue virus envelope studied by molecular dynamics simulations , 2017, Journal of physics. Condensed matter : an Institute of Physics journal.

[14]  K. Schulten,et al.  Contributions of Charged Residues in Structurally Dynamic Capsid Surface Loops to Rous Sarcoma Virus Assembly , 2016, Journal of Virology.

[15]  Benjamin A. Himes,et al.  Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site , 2016, Nature Communications.

[16]  Daniel S. D. Larsson,et al.  Virus Capsid Dissolution Studied by Microsecond Molecular Dynamics Simulations , 2012, PLoS Comput. Biol..

[17]  Gregory A Voth,et al.  Multiscale computer simulation of the immature HIV-1 virion. , 2010, Biophysical journal.

[18]  Joshua S. Mincer,et al.  Modeling the dynamics and kinetics of HIV-1 Gag during viral assembly , 2018, PLoS ONE.

[19]  Frank Heinrich,et al.  Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations. , 2018, Biochimica et biophysica acta. Biomembranes.

[20]  M. Hagan,et al.  Why Enveloped Viruses Need Cores-The Contribution of a Nucleocapsid Core to Viral Budding. , 2017, Biophysical journal.

[21]  Peter L. Freddolino,et al.  Molecular dynamics simulations of the complete satellite tobacco mosaic virus. , 2006, Structure.

[22]  D. Tieleman,et al.  The MARTINI force field: coarse grained model for biomolecular simulations. , 2007, The journal of physical chemistry. B.

[23]  Sergio Pantano,et al.  MD Simulations of Viruslike Particles with Supra CG Solvation Affordable to Desktop Computers. , 2017, Journal of chemical theory and computation.

[24]  Duncan Poole,et al.  Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 1. Generalized Born , 2012, Journal of chemical theory and computation.

[25]  Samuel T. Jones,et al.  Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism. , 2018 .

[26]  Daniel L. Parton,et al.  Nothing to Sneeze At: A Dynamic and Integrative Computational Model of an Influenza A Virion , 2015, Structure.

[27]  Yuji Sugita,et al.  Multiple program/multiple data molecular dynamics method with multiple time step integrator for large biological systems , 2017, J. Comput. Chem..

[28]  Dmitry Nerukh,et al.  MS2 bacteriophage capsid studied using all-atom molecular dynamics , 2019, Interface Focus.

[29]  B. Montgomery Pettitt,et al.  Phage‐like packing structures with mean field sequence dependence , 2017, J. Comput. Chem..

[30]  M. Cieplak,et al.  Self-assembly of model proteins into virus capsids , 2017, Journal of physics. Condensed matter : an Institute of Physics journal.

[31]  J. P. Grossman,et al.  Anton 2: Raising the Bar for Performance and Programmability in a Special-Purpose Molecular Dynamics Supercomputer , 2014, SC14: International Conference for High Performance Computing, Networking, Storage and Analysis.

[32]  Sergio Pantano,et al.  Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly , 2018, PLoS Comput. Biol..

[33]  D. Mathews,et al.  Accurate SHAPE-directed RNA structure determination , 2009, Proceedings of the National Academy of Sciences.

[34]  A. Zlotnick,et al.  Assembly Properties of Hepatitis B Virus Core Protein Mutants Correlate with Their Resistance to Assembly-Directed Antivirals , 2018, Journal of Virology.

[35]  Chandra S Verma,et al.  Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C , 2019, PLoS pathogens.

[36]  Chandra S Verma,et al.  Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody. , 2019, Structure.

[37]  Mark S.P. Sansom,et al.  The Role of the Membrane in the Structure and Biophysical Robustness of the Dengue Virion Envelope , 2016, Structure.

[38]  M. Hagan.  Modeling Viral Capsid Assembly. , 2013, Advances in chemical physics.

[39]  K. Schulten,et al.  All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits , 2018, eLife.

[40]  Klaus Schulten,et al.  All-Atom Molecular Dynamics of Virus Capsids as Drug Targets , 2016, The journal of physical chemistry letters.

[41]  J. Lepault,et al.  A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion , 2017, Science.

[42]  Klaus Schulten,et al.  Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics , 2013, Nature.

[43]  Yinghao Wu,et al.  A Multiscale Model for the Self-Assembly of Coat Proteins in Bacteriophage MS2 , 2019, J. Chem. Inf. Model..

[44]  P. Smooker,et al.  Investigation of a predicted N-terminal amphipathic α-helix using atomistic molecular dynamics simulation of a complete prototype poliovirus virion. , 2012, Journal of molecular graphics & modelling.

[45]  Aaron T. L. Lun,et al.  COMRADES determines in vivo RNA structures and interactions , 2018, Nature Methods.

[46]  Y. Xiong,et al.  FEZ1 Is Recruited to a Conserved Cofactor Site on Capsid to Promote HIV-1 Trafficking. , 2019, Cell reports.

[47]  Chandra S Verma,et al.  A Funneled Conformational Landscape Governs Flavivirus Fusion Peptide Interaction with Lipid Membranes. , 2018, Journal of chemical theory and computation.

[48]  David van der Spoel,et al.  Screening for the Location of RNA using the Chloride Ion Distribution in Simulations of Virus Capsids. , 2012, Journal of chemical theory and computation.

[49]  Gregory A Voth,et al.  Off-Pathway Assembly: A Broad-Spectrum Mechanism of Action for Drugs That Undermine Controlled HIV-1 Viral Capsid Formation , 2019, Journal of the American Chemical Society.

[50]  K. Schulten,et al.  Physical properties of the HIV-1 capsid from all-atom molecular dynamics simulations , 2017, Nature Communications.

[51]  M. Taiji,et al.  All-Atom Molecular Dynamics Simulations of Entire Virus Capsid Reveal the Role of Ion Distribution in Capsid's Stability. , 2017, The journal of physical chemistry letters.

[52]  D. Hrebík,et al.  Enterovirus particles expel capsid pentamers to enable genome release , 2019, Nature Communications.

[53]  Surbhi Leekha,et al.  General Principles of Antimicrobial Therapy , 2011, Mayo Clinic proceedings.

[54]  Benjamin A. Himes,et al.  In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway , 2016, Nature Communications.

[55]  B. Gerstman,et al.  A cylindrical assembly model and dynamics of the Ebola virus VP40 structural matrix , 2018, Scientific Reports.

[56]  Gregory A Voth,et al.  Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly , 2016, Nature Communications.

[57]  MxB Restricts HIV-1 by Targeting the Tri-hexamer Interface of the Viral Capsid. , 2019, Structure.

[58]  Chandra Verma,et al.  Pushing the Envelope: Dengue Viral Membrane Coaxed into Shape by Molecular Simulations. , 2016, Structure.

[59]  D. Reguera,et al.  Kinetics of empty viral capsid assembly in a minimal model. , 2019, Soft matter.

[60]  John L. Klepeis,et al.  Millisecond-scale molecular dynamics simulations on Anton , 2009, Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis.

[61]  M. Bachmann,et al.  DNA packaging in viral capsids with peptide arms. , 2017, Soft matter.

[62]  M. Beltramello,et al.  A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential , 2017, Cell.

[63]  S. Karabasov,et al.  Complete virus capsid at all-atom resolution: simulations using Molecular Dynamics and hybrid Molecular Dynamics/hydrodynamics methods reveal semipermeable membrane function , 2017 .

[64]  Helmut Grubmüller,et al.  Mechanical properties of the icosahedral shell of southern bean mosaic virus: a molecular dynamics study. , 2009, Biophysical journal.

[65]  Yifan Cheng.  Single-Particle Cryo-EM at Crystallographic Resolution , 2015, Cell.

[66]  K. Schulten,et al.  Quenching protein dynamics interferes with HIV capsid maturation , 2017, Nature Communications.

[67]  D. Rapaport.  Molecular dynamics study of T = 3 capsid assembly , 2017, Journal of Biological Physics.

[68]  Marc C. Johnson,et al.  Inositol phosphates are assembly co-factors for HIV-1 , 2018, Nature.

[69]  Antony K. Chen,et al.  Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane , 2017, Proceedings of the National Academy of Sciences.

[70]  Francisco J. Martinez-Veracoechea,et al.  Design of Multivalent Inhibitors for Preventing Cellular Uptake , 2017, Scientific Reports.