A lattice model for the interpretation of oligonucleotide hybridization experiments

We present a lattice model developed to interpret oligonucleotide hybridization experiments beyond the two-state, all-or-none description. Our model is a statistical extension of the nearest-neighbor model in which all possible combinations of broken and intact base pairs in the duplex state are considered explicitly. The conformational degrees of freedom of unpaired nucleotides in the single-strand or duplex state are modeled as self-avoiding walks of the polymer chain on a cubic lattice. Translational entropy and concentration effects are modeled through a coarser lattice of single-strand sized sites. Introducing a single free parameter for the excess entropy per unpaired nucleotide results in reasonable agreement with experiment. While the model provides a generally applicable tool, we illustrate specifically how it is used to interpret equilibrium and nonequilibrium infrared spectroscopy measurements and validate that the model correctly captures sequence and length dependent effects for sequences up to 18 nucleotides. Model predictions are directly related to experiments through computed melting curves. Calculated free energy surfaces offer insight into the interpretation of temperature-jump measurements of oligonucleotide dehybridization. The model captures the interplay between configurational variation and the enthalpic stabilization of base pairing contacts in the context of a minimalist statistical description of DNA hybridization and offers useful insight beyond the simplest all-or-none picture.