Flexing and folding double helical DNA

DNA base sequence, once thought to be interesting only as a carrier of the genetic blueprint, is now recognized as playing a structural role in modulating the biological activity of genes. Primary sequences of nucleic acid bases describe real three-dimensional structures with properties reflecting those structures. Moreover, the structures are base sequence dependent with individual residues adopting characteristic spatial forms. As a consequence, the double helix can fold into tertiary arrangements, although the deformation is much more gradual and spread over a larger molecular scale than in proteins. As part of an effort to understand how local structural irregularities are translated at the macromolecular level in DNA and recognized by proteins, a series of calculations probing the structure and properties of the double helix have been performed. By combining several computational techniques, complementary information as well as a series of built-in checks and balances for assessing the significance of the findings are obtained. The known sequence dependent bending, twisting, and translation of simple dimeric fragments have been incorporated into computer models of long open DNAs of varying length and chemical composition as well as in closed double helical circles and loops. The extent to which the double helix can be forced to bend and twist is monitored with newly parameterized base sequence dependent elastic energy potentials based on the observed configurations of adjacent base pairs in the B-DNA crystallographic literature.