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Controlled manipulation of long strands
of DNA (cleaving, concatenation, and recombination)
is one of the major bottlenecks in the development of
functional genomic analysis and bioinformatics. It is
generally perceived that DNA manipulation could be facilitated
considerably in confined geometries. A predictive tool
capable of anticipating the structure and dynamics of
DNA molecules in confined systems could be of tremendous
scientific and engineering value. Consider, for example,
if a chromosome length DNA molecule could be trapped
in a 20 nanometer wide channel with minimal physical
damage. Theoretical tools capable of describing the
effects of external fields (surfaces, electric fields,
flow, ultrasound) on the behavior of the molecule offer
hope that effective “threading’ processes
can be devised. The Schwartz, Graham and de Pablo groups
have made considerable progress in the modeling and
simulation of DNA in arbitrary flow fields and in confined
geometries (at the 100-nm length scale). I will work
on developing methods to describe the sub 100-nm length
scale.
I aim to develop the first dynamic coarse
graining algorithm for simulation of DNA. At long length
scales, DNA will be represented by simple, large spherical
segments (measuring tens of nanometers). At short length
scales (e.g. when a DNA molecule approaches a surface),
these segments will be spontaneously broken into smaller,
offspring segments in a dynamic manner. A multitude
of parameters such as the flow geometry, flow rate,
temperature and confinement conditions are known to
affect the polymer conformation, segment-segment and
segment-surface interactions, and if appropriate, reaction
conditions. By developing the capability to model such
systems, the trial-and-error experimental process to
find optimal conditions for single DNA molecule manipulation
may be greatly simplified and better controlled.
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