Physical chemistry of DNA viruses
C. M. Knobler and W. M. Gelbart, Physical chemistry of DNA viruses, Annu. Rev. Phys. Chem. 60, 367-83 (2009).
In this review, Knobler and Gelbart argue the case for the physical basis underlying the fact that genome size and capsid volume scale approximately linearly for a broad range of double-stranded (ds) DNA viruses. This property is associated with the fact that viral DNA genomes are essentially close-packed (hexagonally, locally) in the rigid, pre-formed, shells into which they are packaged by one of their gene products, a super-strong motor protein. From several different theoretical calculations – including phenomenological continuum approaches and molecular dynamics simulations, and from both single-particle and bulk solution experimental measurements of packaging forces and pressures, it is found that DNA self-repulsion is the dominant contribution to genome stress in the capsid, with bending energy of secondary importance. Effects of salt concentrations and genome length are also discussed.
PDFs: annurev.physchem.pdf (5.47 MB)
PNGs: Physical chemistry of DNA viruses.png (191.41 KB)
Research categories: Viruses
Origin of icosahedral symmetry in viruses
R. Zandi, D. Reguera, R. F. Bruinsma, W.M. Gelbart, and J. Rudnick, Origin of icosahedral symmetry in viruses, Proc. Natl. Acad. Sci. (USA) 101, 15556-15560 (2004).
Crick and Watson, in 1956, first argued that viral capsids should either be cylindrical/helical or spherical/icosahedral; six years later, Caspar and Klug extended this argument with the prediction of a discrete hierarchy of increasingly larger icosahedrally-symmetric shells, each containing a successively higher number (T) of inequivalent positions for the 60T capsid protein subunits involved, with T=1,3,4,7,…. Zandi et al. demonstrate how this series of “magic numbers” – which are indeed observed for virtually all spherical viruses whose capsid structures have been determined – arise from simple energy minimization performed for fixed numbers of particles interacting on the surface of a sphere. All of these structures are made up of 12 pentameric groups of proteins, and T-1 hexamers.
PDFs: PNAS 2004.pdf (4.79 MB)
PNGs: Minimum energy structures obtained.png (333.03 KB)
Research categories: Viruses
Viral Capsid Equilibrium Dynamics Reveals Nonuniform Elastic Properties
May, E.R., Aggarwal, A., Klug, W.S., and Brooks III, C.L., “Viral Capsid Equilibrium Dynamics Reveals Nonuniform Elastic Properties”, Biophysical Journal, 100(11):L59–L61 (2011)
The long wavelength, low-frequency modes of motion are the relevant motions for understanding the continuummechanical properties of biomolecules. By examining these low-frequency modes, in the context of a spherical harmonic basisset, we identify four elastic moduli that are required to describe the two-dimensional elastic behavior of capsids. This is incontrast to previous modeling and theoretical studies on elastic shells, which use only the two-dimensional Young’s modulus(Y) and the bending modulus (k) to describe the system. Presumably, the heterogeneity of the structure and the anisotropyof the biomolecular interactions lead to a deviation from the homogeneous, isotropic, linear elastic shell theory. We assign func-tional relevance of the various moduli governing different deformation modes, including a mode primarily sensed in atomic forcemicroscopy nanoindentation experiments. We have performed our analysis on the T 1⁄4 3 cowpea chlorotic mottle virus and ourestimate for the nanoindentation modulus is in accord with experimental measurements.
PDFs: May-BPJ-2011.pdf (10.53 MB)
PNGs: Harmonic spectra of the protein shells of viruses.png (3.18 MB)
Research categories: Viruses, Cellular mechanics
Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential
M. Zasloff, A. Adams, B. Beckerman, A. Campbell, Z. Han, E. Luijten, I. Meza, J. Julander, A. Mishra, W. Qu, J. Taylor, S. Weaver, G. C. L. Wong, “Squalamine as a broad spectrum antiviral with therapeutic potential”, Proc. Nat. Acad. Sci. USA, 108 159
Michael Zasloffa, A. Paige Adams, Bernard Beckerman, Ann Campbell, Ziying Han, Erik Luijten, Isaura Meza, Justin Julander, Abhijit Mishra, Wei Qu, John M. Taylor, Scott C. Weaver, and Gerard C. L. Wong
Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored.
JPEGs: Wong group elucidates antiviral immune system of shark.jpg (188.24 KB)
PDFs: PNAS Zasloff Mishra Wong 2011.pdf (6.61 MB)
Research categories: Viruses, Biological Macromolecules