Viruses are small intracellular parasites that invade the cells of virtually all known organisms. They reproduce by utilizing the cell's machinery to replicate viral proteins and genomic material, generally damaging or killing the host cell in the process; subsequentelly, a large number of newly generated viruses go on to infect other cells. Viruses are responsible for a wide variety of human diseases, ranging from the common (influenza and colds) to the exotic (AIDS, West Nile virus and Zika). Some viruses which are not dangerous to humans can also be exploited in technological applications, in addition, viruses find use in genetic engineering applications and increasingly in the design of new nanomaterials. At the very least, all viruses contain two components: the capsid (a protein shell), and a genome, consisting of either DNA or RNA. Some viruses also include accessory proteins to aid in infection, and in some cases a lipid bilayer to further protect their contents from the environment. The viral life cycle itself is deceivingly simple: viruses enter the cell, typically (but not always) through the interaction of their capsid with a receptor on the cell surface; the virus must then somehow disassemble its capsid to release its genetic material and any necessary helper proteins. The viral genome is then replicated and the proteins it codes for are synthesized to produce the raw material for the production of new viral particles; these new viruses then assemble and bud from the cell either through the membrane or upon cell death.

Spotlight: Viruses Up Close (Jan 2007)

Coarse-grained model of the reovirus core

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made with VMD

Viruses are the cause of many human diseases, from the common cold to AIDS, and medicine is continuously searching for better ways to battle viruses through vaccination or medication. Detailed knowledge of the life cycles of viruses should be useful in the treatment of viral diseases. A key focus of investigations is the virus capsid, a protein coat that protects the viral genome, but also triggers release of the genome and other viral factors upon contact with the body's cells. X-ray crystallography has resolved the average structures of many types of virus capsids, providing the basis for detailed investigations, for example by means of molecular dynamics methods, of capsid dynamical properties, e.g., in assembly and disassembly. Unfortunately, due to their large size most virus capsids are beyond the reach of molecular dynamics simulations, with one notable exception (see the March 2006 highlight "Simulating an Entire Life Form"). This earlier simulation allowed researchers to develop and test a method for coarse-grained molecular dynamics simulations that glosses over atomic detail and, thereby, permits microsecond descriptions of entire viral particles. As reported recently (see also journal cover) such simulations, employing the program NAMD, were applied to the empty capsids of several viruses. These simulations revealed a variety of behaviors, from rapid collapse to high stability, depending on the strength of interactions between the proteins from which capsids are built. The new method offers unprecedented views of capsid dynamics that may assist in battling viral diseases. More information on the simulations can be found on our virus web page.

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Publications Database
  • Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Gongpu Zhao, Juan R. Perilla, Ernest L. Yufenyuy, Xin Meng, Bo Chen, Jiying Ning, Jinwoo Ahn, Angela M. Gronenborn, Klaus Schulten, Christopher Aiken, and Peijun Zhang. Nature, 497:643-646, 2013.
  • Cyclophilin A stabilizes HIV-1 capsid through a novel non-canonical binding site. Chuang Liu, Juan R. Perilla, Jiying Ning, Manman Lu, Guangjin Hou, Ruben Ramalho, Gregory Bedwell, In-Ja Byeon, Jinwoo Ahn, Jiong Shi, Angela Gronenborn, Peter Prevelige, Itay Rousso, Christopher Aiken, Tatyana Polenova, Klaus Schulten, and Peijun Zhang. Nature Communications, 7:10714:(10 pages), 2016.
  • Dynamic allostery governs cyclophylin A-HIV capsid interplay. Manman Lu, Guangjin Hou, Huilan Zhang, Christopher L. Suiter, Jinwoo Ahn, In-Ja L. Byeon, Juan R. Perilla, Christopher J. Langmead, Ivan Hung, Peter L. Gor'kov, Zhehong Gan, William Brey, Christopher Aiken, Peijun Zhang, Klaus Schulten, Angela M. Gronenborn, and Tatyana Polenova. Proceedings of the National Academy of Sciences, USA, 112:14617-14622, 2015.
  • Atomic modeling of an immature retroviral lattice using molecular dynamics and mutagenesis. Boon Chong Goh, Juan R. Perilla, Matthew R. England, Katrina J. Heyrana, Rebecca C. Craven, and Klaus Schulten. Structure, 23:1414-1425, 2015.
  • HIV-1 capsid function is regulated by dynamics: Quantitative atomic-resolution insights by integrating magic-angle-spinning NMR, QM/MM, and MD. Huilan Zhang, Guangjin Hou, Manman Lu, Jinwoo Ahn, In-Ja L. Byeon, Christopher J. Langmead, Juan R. Perilla, Ivan Hung, Peter L. Gor'kov, Zhehong Gan, William W. Brey, David A. Case, Klaus Schulten, Angela M. Gronenborn, and Tatyana Polenova. Journal of the American Chemical Society, 138:14066-14075, 2016.
  • All-atom molecular dynamics of virus capsids as drug targets. Juan R. Perilla, Jodi A. Hadden, Boon Chong Goh, Christopher G. Mayne, and Klaus Schulten. Journal of Physical Chemistry Letters, 7:1836-1844, 2016.
  • Molecular dynamics simulations of the complete satellite tobacco mosaic virus. Peter L. Freddolino, Anton S. Arkhipov, Steven B. Larson, Alexander McPherson, and Klaus Schulten. Structure, 14:437-449, 2006.
  • Stability and dynamics of virus capsids described by coarse-grained modeling. Anton Arkhipov, Peter L. Freddolino, and Klaus Schulten. Structure, 14:1767-1777, 2006.
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