The four-state model of a linear lattice: application to ligand-controlled hybridization of short duplex DNAs

An algorithm for calculating the order-disorder transition of a four-state linear lattice is presented. Recursion schemes for the probabilities of each site along the lattice occupying one of the four possible states were derived following the work of D. Poland (Biopolymers, 1974, Vol. 13, pp. 1859-1871) and H. Tachibana and A. Wada (Biopolymers, 1982, Vol. 21, pp. 1873-1885). The algorithm was parameterized to consider melting of short duplex DNA in the presence of duplex and single-strand binding ligands. Model calculations were performed for two 31 base-pair duplex DNAs with very different percent guanine-cytosine base pairs, and thus very different thermodynamic stabilities. In the absence of ligands, calculated melting curves of the two DNAs under identical solvent conditions and identical concentrations were separated by over 15 degrees C. In the presence of either duplex or single-strand binding ligands, if a sequence dependence to ligand binding is assumed, the melting curves of the two DNAs can be made to coalesce, i.e., stability of the two DNAs can be normalized! This example demonstrates the feasibility of controlling hybridization of short DNAs by sequence specific ligand binding.