Free energy calculations of Watson-Crick base pairing in aqueous solution

The free energy of association of adenine-thymine and guanine-cytosine base pairs is estimated from potential of mean force computations in water usin g the AMBER potential energy function. The results, which lead to free ener gies per hydrogen bond of roughly 2 kcal/mol, highlight the existence of se condary water-bridged minima for both base pairs and also show that adenine -thymine pairs undergo frequent exchanges between canonical and reversed Wa tson-Crick states by contra-rotation of the bases around their common axis.