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.