Despite their simplicity, bacteriophage are viral agents having the specialized ability of manipulating and controlling deoxyribonucleic acid (DNA) molecules in a very precise manner. Prior to attacking a host cell, and crucial to their proliferation, bacteriophage first package their genome into a container, or capsid, having a spatial dimension comparable to the smallest characteristic length scale of DNA. The packaging step represents a remarkable feat mediated by a biological motor, which must overcome a large, resistive force as the amount of loaded DNA reaches the entirety of the viral genome, making this one of the most powerful molecular motors known to date. While only the first and last snapshots of the process (unpackaged and packaged DNA, respectively) have been captured by experiments, the in-between images have yet to be acquired to understand the mechanism behind DNA packing in capsids, and more specifically, the operation of the molecular motor.
My project in Juan de Pablo’s group aims to address the in-between snapshots of bacteriophage packing, and follow through the subsequent stages of viral infection, by using computer simulation methods. Several considerations that will be given to the problem include geometrical requirements, associated forces and pressures in the system, and the effects of hydrodynamics, salt concentration, as well as electrostatic interactions on the process. For convenience and practicality, most computational work done previously in this area employ a heavily coarse-grained model that is likely to overlook essential details in describing the formation of the genome/capsid co-assembly on smaller length scales. We propose to use an improved mesoscopic model for DNA to help answer questions posed by the viral packaging problem and provide insights for future experimental work. Our understanding of the operation of the molecular motor and the interactions of the genome with the capsid will shed light on the general problem of exonucleolytic manipulation of DNA, such as in the design and optimization of nanoscopic devices for biotechnological applications.