Generalized Poland–Scheraga model for DNA hybridization

The Poland–Scheraga (PS) model for the helix–coil transition of DNA considers the statistical mechanics of the binding (or hybridization) of two complementary strands of DNA of equal length, with the restriction that only bases with the same index along the strands are allowed to bind. In this article, we extend this model by relaxing these constraints: We propose a generalization of the PS model that allows for the binding of two strands of unequal lengths N 1 and N 2 with unrelated sequences. We study in particular (i) the effect of mismatches on the hybridization of complementary strands, (ii) the hybridization of noncomplementary strands (as resulting from point mutations) of unequal lengths N 1 and N 2 . The use of a Fixman–Freire scheme scales down the computational complexity of our algorithm from O ( N   1 2N   2 2 ) to O ( N 1 N 2 ). The simulation of complementary strands of a few kilo base pairs yields results almost identical to the PS model. For short strands of equal or unequal lengths, the binding displays a strong sensitivity to mutations. This model may be relevant to the experimental protocol in DNA microarrays, and more generally to the molecular recognition of DNA fragments. It also provides a physical implementation of sequence alignments. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004