Keywords

Monte Carlo methods, Free energy, Thermodynamics, DNA microarrays, Chemical bonding, Nucleotides, Coarse-grain model, DNA hybridization, Proteins, Biological physics

Abstract

Hybridization of single-stranded DNA (ssDNA) targets to surface-tethered ssDNA probes was simulated using an advanced coarse-grain model to identify key factors that influence the accuracy of DNA microarrays. Comparing behavior in the bulk and on the surface showed, contrary to previous assumptions, that hybridization on surfaces is more thermodynamically favorable than in the bulk. In addition, the effects of stretching or compressing the probe strand were investigated as a model system to test the hypothesis that improving surface hybridization will improve microarray performance. The results in this regard indicate that selectivity can be increased by reducing overall sensitivity by a small degree. Taken as a whole, the results suggest that current methods to enhance microarray performance by seeking to improve hybridization on the surface may not yield the desired outcomes.

Original Publication Citation

T. J. Schmitt and T. A. Knotts IV, Thermodynamics of DNA Hybridization on Surfaces, J. Chem. Phys., 134, 205105 (2011).