All-Atom Molecular Dynamics of Virus Capsids as Drug Targets

Perilla, Juan R.; Hadden, Jodi A.; Goh, Boon Chong; Mayne, Christopher G.; Schulten, Klaus

doi:10.1021/acs.jpclett.6b00517

Title: All-Atom Molecular Dynamics of Virus Capsids as Drug Targets

Journal Article · Wed May 04 00:00:00 EDT 2016 · Journal of Physical Chemistry Letters

DOI:https://doi.org/10.1021/acs.jpclett.6b00517· OSTI ID:1250973

Perilla, Juan R. ^[1]; Hadden, Jodi A. ^[1]; Goh, Boon Chong ^[1]; Mayne, Christopher G. ^[1]; Schulten, Klaus ^[1]

Beckman Institute, and ‡Department of Physics, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States

Virus capsids are protein shells that package the viral genome. Although their morphology and biological functions can vary markedly, capsids often play critical roles in regulating viral infection pathways. A detailed knowledge of virus capsids, including their dynamic structure, interactions with cellular factors, and the specific roles that they play in the replication cycle, is imperative for the development of antiviral therapeutics. The following Perspective introduces an emerging area of computational biology that focuses on the dynamics of virus capsids and capsid–protein assemblies, with particular emphasis on the effects of small-molecule drug binding on capsid structure, stability, and allosteric pathways. When performed at chemical detail, molecular dynamics simulations can reveal subtle changes in virus capsids induced by drug molecules a fraction of their size. Finally, the current challenges of performing all-atom capsid–drug simulations are discussed, along with an outlook on the applicability of virus capsid simulations to reveal novel drug targets.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Univ. of Illinois at Urbana-Champaign, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1250973

Alternate ID(s):: OSTI ID: 1344922

Journal Information:: Journal of Physical Chemistry Letters, Journal Name: Journal of Physical Chemistry Letters Vol. 7 Journal Issue: 10; ISSN 1948-7185

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 63 works

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References (77)

Visualization of a missing link in retrovirus capsid assembly Cardone, Giovanni; Purdy, John G.; Cheng, Naiqian Nature, Vol. 457, Issue 7230 https://doi.org/10.1038/nature07724	journal	February 2009
Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of p K _a Values Søndergaard, Chresten R.; Olsson, Mats H. M.; Rostkowski, Michał Journal of Chemical Theory and Computation, Vol. 7, Issue 7 https://doi.org/10.1021/ct200133y	journal	June 2011
Twenty-five years of nucleic acid simulations Cheatham, Thomas E.; Case, David A. Biopolymers https://doi.org/10.1002/bip.22331	journal	June 2013
Representation of Ion–Protein Interactions Using the Drude Polarizable Force-Field Li, Hui; Ngo, Van; Da Silva, Mauricio Chagas The Journal of Physical Chemistry B, Vol. 119, Issue 29 https://doi.org/10.1021/jp510560k	journal	September 2014
Virus assembly, allostery and antivirals Zlotnick, Adam; Mukhopadhyay, Suchetana Trends in Microbiology, Vol. 19, Issue 1 https://doi.org/10.1016/j.tim.2010.11.003	journal	January 2011
Constant pH Molecular Dynamics Reveals pH-Modulated Binding of Two Small-Molecule BACE1 Inhibitors Ellis, Christopher R.; Tsai, Cheng-Chieh; Hou, Xinjun The Journal of Physical Chemistry Letters, Vol. 7, Issue 6 https://doi.org/10.1021/acs.jpclett.6b00137	journal	February 2016
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility Morris, Garrett M.; Huey, Ruth; Lindstrom, William Journal of Computational Chemistry, Vol. 30, Issue 16 https://doi.org/10.1002/jcc.21256	journal	December 2009
Physical Principles in the Construction of Regular Viruses Caspar, D. L. D.; Klug, A. Cold Spring Harbor Symposia on Quantitative Biology, Vol. 27, Issue 0 https://doi.org/10.1101/SQB.1962.027.001.005	journal	January 1962
Recent Advances in Polarizable Force Fields for Macromolecules: Microsecond Simulations of Proteins Using the Classical Drude Oscillator Model Huang, Jing; Lopes, Pedro E. M.; Roux, Benoît The Journal of Physical Chemistry Letters, Vol. 5, Issue 18 https://doi.org/10.1021/jz501315h	journal	September 2014
Hepatitis B virus and Homo sapiens proteomewide analysis: A profusion of viral peptide overlaps in neuron-specific human proteins Kanduc, Darja Biologics: Targets & Therapy https://doi.org/10.2147/BTT.S8890	journal	April 2010
Compensatory Substitutions in the HIV-1 Capsid Reduce the Fitness Cost Associated with Resistance to a Capsid-Targeting Small-Molecule Inhibitor Shi, Jiong; Zhou, Jing; Halambage, Upul D. Journal of Virology, Vol. 89, Issue 1 https://doi.org/10.1128/JVI.01411-14	journal	October 2014
Systematic Parametrization of Polarizable Force Fields from Quantum Chemistry Data Wang, Lee-Ping; Chen, Jiahao; Van Voorhis, Troy Journal of Chemical Theory and Computation, Vol. 9, Issue 1 https://doi.org/10.1021/ct300826t	journal	November 2012
Contributions of Charged Residues in Structurally Dynamic Capsid Surface Loops to Rous Sarcoma Virus Assembly Heyrana, Katrina J.; Goh, Boon Chong; Perilla, Juan R. Journal of Virology, Vol. 90, Issue 12 https://doi.org/10.1128/JVI.00378-16	journal	April 2016
Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics Zhao, Gongpu; Perilla, Juan R.; Yufenyuy, Ernest L. Nature, Vol. 497, Issue 7451 https://doi.org/10.1038/nature12162	journal	May 2013
The SAMPL4 host–guest blind prediction challenge: an overview Muddana, Hari S.; Fenley, Andrew T.; Mobley, David L. Journal of Computer-Aided Molecular Design, Vol. 28, Issue 4 https://doi.org/10.1007/s10822-014-9735-1	journal	March 2014
A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly Stray, S. J.; Bourne, C. R.; Punna, S. Proceedings of the National Academy of Sciences, Vol. 102, Issue 23 https://doi.org/10.1073/pnas.0409732102	journal	May 2005
The ligand binding mechanism to purine nucleoside phosphorylase elucidated via molecular dynamics and machine learning Decherchi, Sergio; Berteotti, Anna; Bottegoni, Giovanni Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms7155	journal	January 2015
Structural basis of HIV-1 capsid recognition by PF74 and CPSF6 Bhattacharya, Akash; Alam, Steven L.; Fricke, Thomas Proceedings of the National Academy of Sciences, Vol. 111, Issue 52 https://doi.org/10.1073/pnas.1419945112	journal	December 2014
HIV-1 uncoating: connection to nuclear entry and regulation by host proteins Ambrose, Zandrea; Aiken, Christopher Virology, Vol. 454-455 https://doi.org/10.1016/j.virol.2014.02.004	journal	April 2014
Using Situs for the integration of multi-resolution structures Wriggers, Willy Biophysical Reviews, Vol. 2, Issue 1 https://doi.org/10.1007/s12551-009-0026-3	journal	January 2010
Automation of the CHARMM General Force Field (CGenFF) I: Bond Perception and Atom Typing Vanommeslaeghe, K.; MacKerell, A. D. Journal of Chemical Information and Modeling, Vol. 52, Issue 12 https://doi.org/10.1021/ci300363c	journal	November 2012
Computation-Guided Discovery of Influenza Endonuclease Inhibitors Chen, Eric; Swift, Robert V.; Alderson, Nazilla ACS Medicinal Chemistry Letters, Vol. 5, Issue 1 https://doi.org/10.1021/ml4003474	journal	November 2013
CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields Vanommeslaeghe, K.; Hatcher, E.; Acharya, C. Journal of Computational Chemistry https://doi.org/10.1002/jcc.21367	journal	January 2009
Molecular Architecture of the Retroviral Capsid Perilla, Juan R.; Gronenborn, Angela M. Trends in Biochemical Sciences, Vol. 41, Issue 5 https://doi.org/10.1016/j.tibs.2016.02.009	journal	May 2016
MATCH: An atom-typing toolset for molecular mechanics force fields Yesselman, Joseph D.; Price, Daniel J.; Knight, Jennifer L. Journal of Computational Chemistry, Vol. 33, Issue 2 https://doi.org/10.1002/jcc.21963	journal	November 2011
Classical Electrostatics for Biomolecular Simulations Cisneros, G. Andrés; Karttunen, Mikko; Ren, Pengyu Chemical Reviews, Vol. 114, Issue 1 https://doi.org/10.1021/cr300461d	journal	August 2013
Constant-pH Hybrid Nonequilibrium Molecular Dynamics–Monte Carlo Simulation Method Chen, Yunjie; Roux, Benoît Journal of Chemical Theory and Computation, Vol. 11, Issue 8 https://doi.org/10.1021/acs.jctc.5b00261	journal	July 2015
X-Ray Structures of the Hexameric Building Block of the HIV Capsid Pornillos, Owen; Ganser-Pornillos, Barbie K.; Kelly, Brian N. Cell, Vol. 137, Issue 7 https://doi.org/10.1016/j.cell.2009.04.063	journal	June 2009
Rapid parameterization of small molecules using the force field toolkit Mayne, Christopher G.; Saam, Jan; Schulten, Klaus Journal of Computational Chemistry, Vol. 34, Issue 32 https://doi.org/10.1002/jcc.23422	journal	September 2013
Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome Šponer, Jiří; Banáš, Pavel; Jurečka, Petr The Journal of Physical Chemistry Letters, Vol. 5, Issue 10 https://doi.org/10.1021/jz500557y	journal	May 2014
Development and testing of a general amber force field Wang, Junmei; Wolf, Romain M.; Caldwell, James W. Journal of Computational Chemistry, Vol. 25, Issue 9 https://doi.org/10.1002/jcc.20035	journal	January 2004
Small-Molecule Effectors of Hepatitis B Virus Capsid Assembly Give Insight into Virus Life Cycle Bourne, C.; Lee, S.; Venkataiah, B. Journal of Virology, Vol. 82, Issue 20 https://doi.org/10.1128/JVI.01360-08	journal	August 2008
Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges Vanommeslaeghe, K.; Raman, E. Prabhu; MacKerell, A. D. Journal of Chemical Information and Modeling, Vol. 52, Issue 12 https://doi.org/10.1021/ci3003649	journal	November 2012
HIV-1 assembly, release and maturation Freed, Eric O. Nature Reviews Microbiology, Vol. 13, Issue 8 https://doi.org/10.1038/nrmicro3490	journal	June 2015
Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion Zeng, Xiancheng; Mukhopadhyay, Suchetana; Brooks, Charles L. Proceedings of the National Academy of Sciences, Vol. 112, Issue 7 https://doi.org/10.1073/pnas.1414190112	journal	February 2015
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Flexible Fitting of Atomic Structures into Electron Microscopy Maps Using Molecular Dynamics Trabuco, Leonardo G.; Villa, Elizabeth; Mitra, Kakoli Structure, Vol. 16, Issue 5 https://doi.org/10.1016/j.str.2008.03.005	journal	May 2008
Structural Convergence between Cryo-EM and NMR Reveals Intersubunit Interactions Critical for HIV-1 Capsid Function Byeon, In-Ja L.; Meng, Xin; Jung, Jinwon Cell, Vol. 139, Issue 4 https://doi.org/10.1016/j.cell.2009.10.010	journal	November 2009
Atomic-level modelling of the HIV capsid Pornillos, Owen; Ganser-Pornillos, Barbie K.; Yeager, Mark Nature, Vol. 469, Issue 7330 https://doi.org/10.1038/nature09640	journal	January 2011
Molecular dynamics simulations and drug discovery Durrant, Jacob D.; McCammon, J. Andrew BMC Biology, Vol. 9, Issue 1 https://doi.org/10.1186/1741-7007-9-71	journal	October 2011
Two Pathways Mediate Interdomain Allosteric Regulation in Pin1 Guo, Jingjing; Pang, Xiaodong; Zhou, Huan-Xiang Structure, Vol. 23, Issue 1 https://doi.org/10.1016/j.str.2014.11.009	journal	January 2015
Characterization of Poliovirus Variants Selected for Resistance to the Antiviral Compound V-073 Liu, Hong-Mei; Roberts, Jason A.; Moore, Deborah Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 11 https://doi.org/10.1128/AAC.00539-12	journal	August 2012
HIV-1 capsid: the multifaceted key player in HIV-1 infection Campbell, Edward M.; Hope, Thomas J. Nature Reviews Microbiology, Vol. 13, Issue 8 https://doi.org/10.1038/nrmicro3503	journal	July 2015
The future of molecular dynamics simulations in drug discovery Borhani, David W.; Shaw, David E. Journal of Computer-Aided Molecular Design, Vol. 26, Issue 1 https://doi.org/10.1007/s10822-011-9517-y	journal	December 2011
Neuraminidase Inhibitors for Influenza Moscona, Anne New England Journal of Medicine, Vol. 353, Issue 13 https://doi.org/10.1056/NEJMra050740	journal	September 2005
Comparative Protein Structure Modeling Using Modeller Eswar, Narayanan; Webb, Ben; Marti-Renom, Marc A. Current Protocols in Bioinformatics, Vol. 15, Issue 1 https://doi.org/10.1002/0471250953.bi0506s15	journal	September 2006
Host Cofactors and Pharmacologic Ligands Share an Essential Interface in HIV-1 Capsid That Is Lost upon Disassembly Price, Amanda J.; Jacques, David A.; McEwan, William A. PLoS Pathogens, Vol. 10, Issue 10 https://doi.org/10.1371/journal.ppat.1004459	journal	October 2014
The Future of HIV-1 Therapeutics: Resistance Is Futile? Torbett, Bruce E.; Goodsell, David S.; Richman, Douglas D. Current Topics in Microbiology and Immunology https://doi.org/10.1007/978-3-319-18518-7	book	January 2015
All-atom polarizable force field for DNA based on the classical drude oscillator model Savelyev, Alexey; MacKerell, Alexander D. Journal of Computational Chemistry, Vol. 35, Issue 16 https://doi.org/10.1002/jcc.23611	journal	April 2014
Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection Taguwa, Shuhei; Maringer, Kevin; Li, Xiaokai Cell, Vol. 163, Issue 5 https://doi.org/10.1016/j.cell.2015.10.046	journal	November 2015
Global Structural Changes in Hepatitis B Virus Capsids Induced by the Assembly Effector HAP1 Bourne, C. R.; Finn, M. G.; Zlotnick, A. Journal of Virology, Vol. 80, Issue 22 https://doi.org/10.1128/JVI.00933-06	journal	August 2006
HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention Blair, Wade S.; Pickford, Chris; Irving, Stephen L. PLoS Pathogens, Vol. 6, Issue 12 https://doi.org/10.1371/journal.ppat.1001220	journal	December 2010
X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability Gres, Anna T.; Kirby, Karen A.; KewalRamani, Vineet N. Science, Vol. 349, Issue 6243 https://doi.org/10.1126/science.aaa5936	journal	June 2015
Dynamic allostery governs cyclophilin A–HIV capsid interplay Lu, Manman; Hou, Guangjin; Zhang, Huilan Proceedings of the National Academy of Sciences, Vol. 112, Issue 47 https://doi.org/10.1073/pnas.1516920112	journal	November 2015
Polarizable Atomic Multipole-Based AMOEBA Force Field for Proteins Shi, Yue; Xia, Zhen; Zhang, Jiajing Journal of Chemical Theory and Computation, Vol. 9, Issue 9 https://doi.org/10.1021/ct4003702	journal	August 2013
Macromolecular Modeling with Rosetta Das, Rhiju; Baker, David Annual Review of Biochemistry, Vol. 77, Issue 1 https://doi.org/10.1146/annurev.biochem.77.062906.171838	journal	June 2008
Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies Han, Yun; Hou, Guangjin; Suiter, Christopher L. Journal of the American Chemical Society, Vol. 135, Issue 47 https://doi.org/10.1021/ja406907h	journal	November 2013
Capsid proteins of enveloped viruses as antiviral drug targets Klumpp, Klaus; Crépin, Thibaut Current Opinion in Virology, Vol. 5 https://doi.org/10.1016/j.coviro.2014.02.002	journal	April 2014
pH-REMD Simulations Indicate That the Catalytic Aspartates of HIV-1 Protease Exist Primarily in a Monoprotonated State McGee, T. Dwight; Edwards, Jesse; Roitberg, Adrian E. The Journal of Physical Chemistry B, Vol. 118, Issue 44 https://doi.org/10.1021/jp504011c	journal	October 2014
Molecular dynamics simulations of large macromolecular complexes Perilla, Juan R.; Goh, Boon Chong; Cassidy, C. Keith Current Opinion in Structural Biology, Vol. 31 https://doi.org/10.1016/j.sbi.2015.03.007	journal	April 2015
Cyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site Liu, Chuang; Perilla, Juan R.; Ning, Jiying Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms10714	journal	March 2016
A model for cofactor use during HIV-1 reverse transcription and nuclear entry Hilditch, Laura; Towers, Greg J. Current Opinion in Virology, Vol. 4 https://doi.org/10.1016/j.coviro.2013.11.003	journal	February 2014
Toward Improved Force-Field Accuracy through Sensitivity Analysis of Host-Guest Binding Thermodynamics Yin, Jian; Fenley, Andrew T.; Henriksen, Niel M. The Journal of Physical Chemistry B, Vol. 119, Issue 32 https://doi.org/10.1021/acs.jpcb.5b04262	journal	July 2015
ViennaRNA Package 2.0 Lorenz, Ronny; Bernhart, Stephan H.; Höner zu Siederdissen, Christian Algorithms for Molecular Biology, Vol. 6, Issue 1 https://doi.org/10.1186/1748-7188-6-26	journal	November 2011
VIPERdb2: an enhanced and web API enabled relational database for structural virology Carrillo-Tripp, M.; Shepherd, C. M.; Borelli, I. A. Nucleic Acids Research, Vol. 37, Issue Database https://doi.org/10.1093/nar/gkn840	journal	January 2009
Constant pH molecular dynamics of proteins in explicit solvent with proton tautomerism: Explicit Solvent CPHMD of Proteins Goh, Garrett B.; Hulbert, Benjamin S.; Zhou, Huiqing Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 7 https://doi.org/10.1002/prot.24499	journal	January 2014
Dynamical networks in tRNA:protein complexes Sethi, A.; Eargle, J.; Black, A. A. Proceedings of the National Academy of Sciences, Vol. 106, Issue 16 https://doi.org/10.1073/pnas.0810961106	journal	April 2009
NetworkView: 3D display and analysis of protein{middle dot}RNA interaction networks Eargle, J.; Luthey-Schulten, Z. Bioinformatics, Vol. 28, Issue 22 https://doi.org/10.1093/bioinformatics/bts546	journal	September 2012
Computational approaches to mapping allosteric pathways Feher, Victoria A.; Durrant, Jacob D.; Van Wart, Adam T. Current Opinion in Structural Biology, Vol. 25 https://doi.org/10.1016/j.sbi.2014.02.004	journal	April 2014
H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations Anandakrishnan, R.; Aguilar, B.; Onufriev, A. V. Nucleic Acids Research, Vol. 40, Issue W1 https://doi.org/10.1093/nar/gks375	journal	May 2012
Atomic Modeling of an Immature Retroviral Lattice Using Molecular Dynamics and Mutagenesis Goh, Boon Chong; Perilla, Juan R.; England, Matthew R. Structure, Vol. 23, Issue 8 https://doi.org/10.1016/j.str.2015.05.017	journal	August 2015
Rational Prediction with Molecular Dynamics for Hit Identification E. Nichols, Sara; V. Swift, Robert; E. Amaro, Rommie Current Topics in Medicinal Chemistry, Vol. 12, Issue 18 https://doi.org/10.2174/156802612804910313	journal	September 2012
Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Infection by Virus Capsid Destabilization Shi, J.; Zhou, J.; Shah, V. B. Journal of Virology, Vol. 85, Issue 1 https://doi.org/10.1128/JVI.01406-10	journal	October 2010
Cyclophilin A: a key player for human disease Nigro, P.; Pompilio, G.; Capogrossi, M. C. Cell Death & Disease, Vol. 4, Issue 10 https://doi.org/10.1038/cddis.2013.410	journal	October 2013
Systematic Improvement of a Classical Molecular Model of Water Wang, Lee-Ping; Head-Gordon, Teresa; Ponder, Jay W. The Journal of Physical Chemistry B, Vol. 117, Issue 34 https://doi.org/10.1021/jp403802c	journal	August 2013
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Constant pH Replica Exchange Molecular Dynamics in Explicit Solvent Using Discrete Protonation States: Implementation, Testing, and Validation Swails, Jason M.; York, Darrin M.; Roitberg, Adrian E. Journal of Chemical Theory and Computation, Vol. 10, Issue 3 https://doi.org/10.1021/ct401042b	journal	February 2014

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