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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.
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