Current Research Projects
DNA Melting and Hybridization
The recent development of DNA sensor microarrays has the potential to
significantly benefit important applications, such as mutation detection,
RNA expression and genetic sequencing. DNA sensors are composed of
single-stranded DNA oligomers bound to a surface. The development of this
technology relies on knowledge of DNA denaturation or ``melting'' and
hybridization transitions, and their sensitivity to many variables has left
several questions unanswered, such as the mechanism by which changes in
physical environment between solution and bound DNA act to influence
hybridization, or competitive adsorption of nearly identical sequences.
DNA melting is a phenomenon that occurs when hybridized double-stranded DNA
helices dissociate into single-stranded DNA coils. The thermodynamic
melting temperature is defined as the temperature at which the
double-strand is exactly half-dissociated and can be measured quite
accurately experimentally. However, the mechanisms and structures
governing the melting process are less well understood.
The application of a simplified model with one interaction site to
represent the base and another site for the phosphate + sugar backbone
allows the investigation of melting and rehybridization transitions. The
tendency for strands to misalign is also captured with this approach in a
natural way. Monte Carlo simulations using configurational bias Monte
Carlo (CBMC) and self-adapting fixed-endpoint CBMC allow the efficient
sampling of phase space for these systems.
The image is of two complementary 10-nucleotide oligomers from work by Nick Tito.
Tunable Supercritical Fluid Separation Systems
Most chemical processes involve solvents and the high cost of separating
reactants, products, catalyst and solvents and the negative environmental
costs of today's solvents are motivation to develop tunable and
environmentally benign solvent systems and chemical processes. These
processes attempt to use fairly innocuous materials such as supercritical
carbon dioxide and polyethylene glycol to achieve what traditional
processes do with more detrimental materials. Unfortunately, the solvating
power of supercritical fluids is generally lower than that of liquid
solvents. Through laborious experiments it has been found that their
performance can be improved. For example, it has been observed that small
amounts of cosolvents or ``entrainers'' can greatly enhance the solvating
power and selectivity of supercritical solvents, but it is difficult to
determine their effect without actually carrying out the experiment. Monte
Carlo molecular simulations allow the efficient modeling of such systems
with the goal of optimizing solvation conditions. This is done by carrying
out calculations with varying thermodynamic (e.g. temperature and/or
pressure) conditions and compositions.
Shown here is a mixture of poly(ethylene glycol) (thin bonds) and ethyl benzene (spheres) in contact with supercritical carbon dioxide (thick bonds) from work by Julian Peters.