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Nat Commun. 2016 May 13;7:11568. doi: 10.1038/ncomms11568.

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.

Author information

1
Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, The University of Chicago, Chicago, Illinois 60637, USA.
2
Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
3
Division of Biology, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.
4
Howard Hughes Medical Institute, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125, USA.
5
Center for Membrane Biology, Cardiovascular Research Center, and Division of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.

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.

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