Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

This content will become publicly available on Wed Jan 22 00:00:00 EST 2025

Title: Hexagonal Lattices of HIV Capsid Proteins Explored by Simulations Based on a Thermodynamically Consistent Model

Abstract

HIV capsid proteins (CAs) may self-assemble into a variety of shapes under in vivo and in vitro conditions. Here, we employed simulations based on a residue-level coarse-grained (CG) model with full conformational flexibility to investigate hexagonal lattices, which are the underlying structural pattern for CA aggregations. Facilitated by enhanced sampling simulations to rigorously calculate CA dimerization and polymerization affinities, we calibrated our model to reproduce the experimentally measured affinities. Here using the calibrated model, we performed unbiased simulations on several large systems consisting of 1512 CA subunits, allowing reversible binding and unbinding of the CAs in a thermodynamically consistent manner. In one simulation, a preassembled hexagonal CA sheet developed spontaneous curvatures reminiscent of those observed in experiments, and the edges of the sheet exhibited local curvatures larger than those of the interior. In other simulations starting with randomly distributed CAs at different concentrations, existing CA assemblies grew by binding free capsomeres to the edges and by merging with other assemblies. At high CA concentrations, rapid establishment of predominant aggregates was followed by much slower adjustments toward more regular hexagonal lattices, with increasing numbers of intact CA hexamers and pentamers being formed. Our approach of adapting a general CG model tomore » specific systems by using experimental binding data represents a practical and effective strategy for simulating and elucidating intricate protein aggregations.« less

Authors:
ORCiD logo [1]; ORCiD logo [2]
+ Show Author Affiliations
  1. Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, IN (United States)
  2. Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, IN (United States); Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Publication Date:
Research Org.:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); US Air Force Office of Scientific Research (AFOSR)
OSTI Identifier:
2315092
Report Number(s):
LLNL-JRNL-848533
Journal ID: ISSN 1520-6106; 1073137
Grant/Contract Number:  
AC52-07NA27344; FA9550-13-1-0150
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Physical Chemistry. B
Additional Journal Information:
Journal Volume: 128; Journal Issue: 4; Journal ID: ISSN 1520-6106
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Sha, Hao, and Zhu, Fangqiang. Hexagonal Lattices of HIV Capsid Proteins Explored by Simulations Based on a Thermodynamically Consistent Model. United States: N. p., 2024. Web. doi:10.1021/acs.jpcb.3c06881.
Copy to clipboard
Sha, Hao, & Zhu, Fangqiang. Hexagonal Lattices of HIV Capsid Proteins Explored by Simulations Based on a Thermodynamically Consistent Model. United States. https://doi.org/10.1021/acs.jpcb.3c06881
Copy to clipboard
Sha, Hao, and Zhu, Fangqiang. Mon . "Hexagonal Lattices of HIV Capsid Proteins Explored by Simulations Based on a Thermodynamically Consistent Model". United States. https://doi.org/10.1021/acs.jpcb.3c06881.
Copy to clipboard
@article{osti_2315092,
title = {Hexagonal Lattices of HIV Capsid Proteins Explored by Simulations Based on a Thermodynamically Consistent Model},
author = {Sha, Hao and Zhu, Fangqiang},
abstractNote = {HIV capsid proteins (CAs) may self-assemble into a variety of shapes under in vivo and in vitro conditions. Here, we employed simulations based on a residue-level coarse-grained (CG) model with full conformational flexibility to investigate hexagonal lattices, which are the underlying structural pattern for CA aggregations. Facilitated by enhanced sampling simulations to rigorously calculate CA dimerization and polymerization affinities, we calibrated our model to reproduce the experimentally measured affinities. Here using the calibrated model, we performed unbiased simulations on several large systems consisting of 1512 CA subunits, allowing reversible binding and unbinding of the CAs in a thermodynamically consistent manner. In one simulation, a preassembled hexagonal CA sheet developed spontaneous curvatures reminiscent of those observed in experiments, and the edges of the sheet exhibited local curvatures larger than those of the interior. In other simulations starting with randomly distributed CAs at different concentrations, existing CA assemblies grew by binding free capsomeres to the edges and by merging with other assemblies. At high CA concentrations, rapid establishment of predominant aggregates was followed by much slower adjustments toward more regular hexagonal lattices, with increasing numbers of intact CA hexamers and pentamers being formed. Our approach of adapting a general CG model to specific systems by using experimental binding data represents a practical and effective strategy for simulating and elucidating intricate protein aggregations.},
doi = {10.1021/acs.jpcb.3c06881},
journal = {Journal of Physical Chemistry. B},
number = 4,
volume = 128,
place = {United States},
year = {Mon Jan 22 00:00:00 EST 2024},
month = {Mon Jan 22 00:00:00 EST 2024}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
This content will become publicly available on January 22, 2025
Publisher's Version of Record
https://doi.org/10.1021/acs.jpcb.3c06881
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Assembly and Analysis of Conical Models for the HIV-1 Core
journal, January 1999

Structural organization of authentic, mature HIV-1 virions and cores
journal, April 2003

Maturation of retroviruses
journal, June 2019

Assembly of recombinant human immunodeficiency virus type 1 capsid protein in vitro
journal, August 1992

Image reconstructions of helical assemblies of the HIV-1 CA protein
journal, September 2000

  • Li, Su; Hill, Christopher P.; Sundquist, Wesley I.
  • Nature, Vol. 407, Issue 6802
  • DOI: 10.1038/35030177

Assembly Properties of the Human Immunodeficiency Virus Type 1 CA Protein
journal, February 2004

HIV Capsid Assembly, Mechanism, and Structure
journal, April 2016

Structure of the Amino-Terminal Core Domain of the HIV-1 Capsid Protein
journal, July 1996

Structure of the Carboxyl-Terminal Dimerization Domain of the HIV-1 Capsid Protein
journal, October 1997

Structure of Full-Length HIV-1 CA: A Model for the Mature Capsid Lattice
journal, October 2007

X-Ray Structures of the Hexameric Building Block of the HIV Capsid
journal, June 2009

Structural Convergence between Cryo-EM and NMR Reveals Intersubunit Interactions Critical for HIV-1 Capsid Function
journal, November 2009

Atomic-level modelling of the HIV capsid
journal, January 2011

  • Pornillos, Owen; Ganser-Pornillos, Barbie K.; Yeager, Mark
  • Nature, Vol. 469, Issue 7330
  • DOI: 10.1038/nature09640

Motions on the Millisecond Time Scale and Multiple Conformations of HIV-1 Capsid Protein: Implications for Structural Polymorphism of CA Assemblies
journal, April 2012

  • Byeon, In-Ja L.; Hou, Guangjin; Han, Yun
  • Journal of the American Chemical Society, Vol. 134, Issue 14
  • DOI: 10.1021/ja300937v

Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics
journal, May 2013

  • Zhao, Gongpu; Perilla, Juan R.; Yufenyuy, Ernest L.
  • Nature, Vol. 497, Issue 7451
  • DOI: 10.1038/nature12162

Unclosed HIV-1 Capsids Suggest a Curled Sheet Model of Assembly
journal, January 2013

  • Yu, Zhiheng; Dobro, Megan J.; Woodward, Cora L.
  • Journal of Molecular Biology, Vol. 425, Issue 1
  • DOI: 10.1016/j.jmb.2012.10.006

Structure and Dynamics of Full-Length HIV-1 Capsid Protein in Solution
journal, October 2013

  • Deshmukh, Lalit; Schwieters, Charles D.; Grishaev, Alexander
  • Journal of the American Chemical Society, Vol. 135, Issue 43
  • DOI: 10.1021/ja406246z

Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein
journal, March 2014

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution
journal, November 2014

  • Schur, Florian K. M.; Hagen, Wim J. H.; Rumlová, Michaela
  • Nature, Vol. 517, Issue 7535
  • DOI: 10.1038/nature13838

X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability
journal, June 2015

  • Gres, Anna T.; Kirby, Karen A.; KewalRamani, Vineet N.
  • Science, Vol. 349, Issue 6243
  • DOI: 10.1126/science.aaa5936

The structure and flexibility of conical HIV-1 capsids determined within intact virions
journal, December 2016

Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site
journal, March 2016

  • Liu, Chuang; Perilla, Juan R.; Ning, Jiying
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms10714

Physical Principles in the Construction of Regular Viruses
journal, January 1962

Inositol phosphates are assembly co-factors for HIV-1
journal, August 2018

A stable immature lattice packages IP 6 for HIV capsid maturation
journal, March 2021

  • Mallery, Donna L.; Kleinpeter, Alex B.; Renner, Nadine
  • Science Advances, Vol. 7, Issue 11
  • DOI: 10.1126/sciadv.abe4716

A conformational switch controlling HIV-1 morphogenesis
journal, January 2000

Physics of Viral Shells
journal, March 2015

Recent advances in coarse-grained modeling of virus assembly
journal, June 2016

Multiscale modelling and simulation of viruses
journal, April 2020

  • Marzinek, Jan K.; Huber, Roland G.; Bond, Peter J.
  • Current Opinion in Structural Biology, Vol. 61
  • DOI: 10.1016/j.sbi.2019.12.019

Model-Based Analysis of Assembly Kinetics for Virus Capsids or Other Spherical Polymers
journal, August 2002

Exploring the Paths of (Virus) Assembly
journal, September 2010

A Trimer of Dimers Is the Basic Building Block for Human Immunodeficiency Virus-1 Capsid Assembly
journal, May 2012

  • Tsiang, Manuel; Niedziela-Majka, Anita; Hung, Magdeleine
  • Biochemistry, Vol. 51, Issue 22
  • DOI: 10.1021/bi300052h

Modeling HIV-1 viral capsid nucleation by dynamical systems
journal, December 2015

Physical properties of the HIV-1 capsid from all-atom molecular dynamics simulations
journal, July 2017

  • Perilla, Juan R.; Schulten, Klaus
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms15959

All-atom virus simulations
journal, August 2018

Are Current Atomistic Force Fields Accurate Enough to Study Proteins in Crowded Environments?
journal, May 2014

Assessing the potential of atomistic molecular dynamics simulations to probe reversible protein-protein recognition and binding
journal, May 2015

  • Abriata, Luciano A.; Dal Peraro, Matteo
  • Scientific Reports, Vol. 5, Issue 1
  • DOI: 10.1038/srep10549

Perspective: Coarse-grained models for biomolecular systems
journal, September 2013

  • Noid, W. G.
  • The Journal of Chemical Physics, Vol. 139, Issue 9
  • DOI: 10.1063/1.4818908

Continuum Theory of Retroviral Capsids
journal, February 2006

Irreversible growth model for virus capsid assembly
journal, September 2006

Invariant Polymorphism in Virus Capsid Assembly
journal, February 2009

  • Nguyen, Hung D.; Reddy, Vijay S.; Brooks III, Charles L.
  • Journal of the American Chemical Society, Vol. 131, Issue 7
  • DOI: 10.1021/ja807730x

Coarse-grained protein-protein stiffnesses and dynamics from all-atom simulations
journal, March 2010

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly
journal, May 2016

  • Grime, John M. A.; Dama, James F.; Ganser-Pornillos, Barbie K.
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms11568

Off-Pathway Assembly: A Broad-Spectrum Mechanism of Action for Drugs That Undermine Controlled HIV-1 Viral Capsid Formation
journal, May 2019

  • Pak, Alexander J.; Grime, John M. A.; Yu, Alvin
  • Journal of the American Chemical Society, Vol. 141, Issue 26
  • DOI: 10.1021/jacs.9b01413

Mechanism of polymorphism and curvature of HIV capsid assemblies probed by 3D simulations with a novel coarse grain model
journal, November 2015

  • Qiao, Xin; Jeon, Jaekyun; Weber, Jeff
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1850, Issue 11
  • DOI: 10.1016/j.bbagen.2015.08.017

Optimizing physical energy functions for protein folding
journal, November 2003

  • Fujitsuka, Yoshimi; Takada, Shoji; Luthey‐Schulten, Zaida A.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 54, Issue 1
  • DOI: 10.1002/prot.10429

A Multiscale Description of Biomolecular Active Matter: The Chemistry Underlying Many Life Processes
journal, March 2017

Critical mechanistic features of HIV-1 viral capsid assembly
journal, January 2023

  • Gupta, Manish; Pak, Alexander J.; Voth, Gregory A.
  • Science Advances, Vol. 9, Issue 1
  • DOI: 10.1126/sciadv.add7434

Performance efficient macromolecular mechanics via sub-nanometer shape based coarse graining
journal, April 2023

Coarse-grained Models for Simulations of Multiprotein Complexes: Application to Ubiquitin Binding
journal, February 2008

Monte Carlo Simulations of HIV Capsid Protein Homodimer
journal, July 2015

Parameter Optimization for Interaction between C-Terminal Domains of HIV-1 Capsid Protein
journal, April 2017

Determining equilibrium constants for dimerization reactions from molecular dynamics simulations
journal, April 2011

  • De Jong, Djurre H.; Schäfer, Lars V.; De Vries, Alex H.
  • Journal of Computational Chemistry, Vol. 32, Issue 9
  • DOI: 10.1002/jcc.21776

Quantifying Protein–Protein Interactions in Molecular Simulations
journal, May 2020

  • Jost Lopez, Alfredo; Quoika, Patrick K.; Linke, Max
  • The Journal of Physical Chemistry B, Vol. 124, Issue 23
  • DOI: 10.1021/acs.jpcb.9b11802

Theory and Simulation of Ion Conduction in the Pentameric GLIC Channel
journal, March 2012

  • Zhu, Fangqiang; Hummer, Gerhard
  • Journal of Chemical Theory and Computation, Vol. 8, Issue 10
  • DOI: 10.1021/ct2009279

Calculating Single-Channel Permeability and Conductance from Transition Paths
journal, January 2019

  • Zhou, Xiaoyan; Zhu, Fangqiang
  • Journal of Chemical Information and Modeling, Vol. 59, Issue 2
  • DOI: 10.1021/acs.jcim.8b00914

Scalable molecular dynamics on CPU and GPU architectures with NAMD
journal, July 2020

  • Phillips, James C.; Hardy, David J.; Maia, Julio D. C.
  • The Journal of Chemical Physics, Vol. 153, Issue 4
  • DOI: 10.1063/5.0014475

On the Hamiltonian replica exchange method for efficient sampling of biomolecular systems: Application to protein structure prediction
journal, May 2002

  • Fukunishi, Hiroaki; Watanabe, Osamu; Takada, Shoji
  • The Journal of Chemical Physics, Vol. 116, Issue 20
  • DOI: 10.1063/1.1472510

Retroviral Capsid Assembly: A Role for the CA Dimer in Initiation
journal, June 2009

  • Purdy, John G.; Flanagan, John M.; Ropson, Ira J.
  • Journal of Molecular Biology, Vol. 389, Issue 2
  • DOI: 10.1016/j.jmb.2009.04.006

Visualization of Single Molecules Building a Viral Capsid Protein Lattice through Stochastic Pathways
journal, July 2020

    Sort by:
    [ × clear filter / sort ]

    Similar Records in DOE PAGES and OSTI.GOV collections: