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Bacteriophage

Bacteriophage are viruses that infect bacteria. Their genomes may be single- or double-stranded RNA or DNA. Our work focuses on the packaging of double-helical DNA molecules into bacteriophage whose genome sizes range from roughly 10 kbp to 100 kbp. The genome in such a virus is driven into a pre-formed capsid by a complex of portal/motor proteins that hydrolyze ATP to generate the necessary force.

There are two reviews of our work on bacteriophage: 

Petrov & Harvey (2008) Biophys J 95:497-502 (PMID 18487310).

Harvey et al. (2009) Phys Chem Chem Phys 11:10553-64 (PMID 20145801).

The full methods behind all of our viral modeling work are found in Harvey et al. (2011) Methods Enzymol 487:513-543 (PMID 21187237).

Here we briefly summarize some of our results on bacteriophage.

   
Figure_1_little

We have carried out a number of simulations to determine how the conformation of the DNA in the mature virus depends on the size and shape of the viral capsid, and by the presence or absence of a large core structure. The figure above shows our model for epsilon 15. (a) The capsid has icosahedral symmetry, except for the large portal/core structure, in green. (b) The genome of the mature virus is organized into a coaxial spool. (c) The groove in the core structure contains some of the double helix; pressure in this region was proposed by Lander et al. (Science 312:1791-95 (2006)) to serve as the mechanism whereby the portal motor is shut down when the capsid is full. The genome adopts a folded toroidal conformation in slightly elongated capsids with small cores such as phi29 (below); this conformation was first proposed on theoretical grounds by Nick Hud (Biophys J 69:1355-62 (1995)).

Figure_3_little

In more elongated capsids, the minimization of elastic bending energy favors conformations with the DNA more or less aligned along the long axis of the capsid, but entropic considerations favor a less ordered organization. The balance between these two tendencies produces the twisted toroidal conformation (below), first proposed by Earnshaw et al. (Cell 14:559-68 (1978)).

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