COAXIAL STACKING OF HELIXES ENHANCES BINDING OF OLIGORIBONUCLEOTIDES AND IMPROVES PREDICTIONS OF RNA FOLDING

An RNA model system consisting of an oligomer binding to a 4-nt overhang at the 5' end of a hairpin stem provides thermodynamic parameters for helix-helix interfaces. In a sequence-dependent manner, oligomers bind up to 1000-fold more tightly adjacent to the hairpin stem than predicted for binding to a free tetramer at 37 degrees C. For the interface (/) in [GRAPHICS] where X and Z are unpaired nucleotides, the additional free energy change, Delta Delta G degrees(37), for binding is roughly the nearest-neighbor Delta G degrees(37), for propagation of an uninterrupted helix of equivalent sequence, [GRAPHICS] When X and Z are omitted, the Delta Delta G degrees(37), is even more favorable by approximate to 1 kcal/mol (1 cal = 4.184j). On average, predictions of 11 RNA secondary structures improve from 67 to 74% accuracy by inclusion of similar stacking contributions.