DNA microarrays are high throughput, parallel assays for determining which genes are present in a sample or the level of expression of the genes.  They have been identified as a key technology in genomic sciences and emergent medical techniques but have not been fully integrated in clinical settings due to the difficulty of obtaining reproducible results. Microarrays function on the principle of DNA hybridization and can only be as reliable as this process is robust.  This study outlines efforts to increase fundamental understanding of hybridization on surfaces.  The simulation results�generated using an advanced, mesoscale model for DNA�offer an unprecedented view of the process.  After briefly explaining the model, several results will be presented.  These include how single nucleotide polymorphisms, the lengths of the oligonucleotides in the probe/target pairs, and the presence of the surface affects hybridization.  Complete mechanistic pathways and energy landscapes of the hybridization process, generated from extensive simulations and advanced techniques, will also be presented.  The results reveal surprising details including the fact that surfaces can actually stabilize hybridization (contrary to common belief) and that the hybridization process on the surface does not proceed through a �zipping� mechanism. Taken as a whole, this work offers new ides which can be used to improve DNA microarray accuracy.

Thermodynamics of DNA hybridization on surfaces

243rd National Meeting (2012)

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