title: Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.
abstract: The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: John M A
authors.initials: JMA
authors.lastname: Grime
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: James F
authors.identifier: http://orcid.org/0000-0001-5891-679X
authors.initials: JF
authors.lastname: Dama
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Barbie K
authors.initials: BK
authors.lastname: Ganser-Pornillos
authors.affiliation: Division of Biology, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.
authors.forename: Cora L
authors.initials: CL
authors.lastname: Woodward
authors.affiliation: Division of Biology, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.|Howard Hughes Medical Institute, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.
authors.forename: Grant J
authors.initials: GJ
authors.lastname: Jensen
authors.affiliation: Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.|Center for Membrane Biology, Cardiovascular Research Center, and Division of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D056004:Molecular Dynamics Simulation; D055503:Protein Multimerization / Q000502:physiology; D012367:RNA, Viral / Q000378:metabolism; D019065:Virus Assembly / Q000502:physiology*
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral