To investigate the effects of sequence on double helix DNA conformations we have developed methods to average over intra- helical degrees of freedom to obtain conformational means and fluctuations. This method is general and yields intra-molecular DNA conformational energies appropriate to study many aspects of the sequence dependence of conformations. In this method, each base pair has been permitted to interact with its neighboring base pairs over a large range of conformations, and the average is extracted in an iterative way. Interaction energies have been evaluated with semi-empirical energy functions. Even though the backbone has not been included in these calculations, interactions among the base pairs alone lead to a strong preference for double helical conformations. The best conformation obtained for the dodecamer, d(CGCGAATTCGCG), compared to the crystal structure, has a RMS deviation of 0.8 A. The co-crystal of this Eco RI recognition site with the Eco RI restriction enzyme shows a substantial helical twist deviation at the AT junction; calculations have confirmed this as the site of largest twist fluctuations in the sequence.
