Base sequence, local helix structure, and macroscopic curvature of A-DNA and B-DNA.

Given a specified DNA sequence and starting with an idealized conformation for the double helix (A-DNA or B-DNA), the dependence of conformational energy on variations in the local geometry of the double helix can be examined by computer modeling. By averaging over all thermally accessible states, it is possible to determine 1) how the optimum local structure differs from the initial idealized conformation and 2) the energetic costs of small structural deformations. This paper describes such a study. Tables are presented for the prediction of helix twist angles and base pair roll angles for both A-DNA and B-DNA when the sequence has been specified. Local deviations of helix parameters from their average values can accumulate to produce a net curvature of the molecule, a curvature that can be sharp enough to be experimentally detectable. As an independent check on the method, the calculations provide predictions for the longitudinal compressibility (Young's modulus) and the average torsional stiffness, both of which are in good agreement with experimental values. In examining the role of sequence-dependent variations in helix structure for the recognition of specific sequences by proteins, we have calculated the energy needed to deform the self-complementary hexanucleotide d(CAATTG) to match the local geometry of d(GAATTC), which is the sequence recognized by the EcoRI restriction endonuclease. That energy would be sufficient to reduce the binding of the incorrect sequence to the protein by over 2 orders of magnitude relative to the correct sequence.