The flexible DNA double helix. II. Superhelix formation.
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Biomedical subjects
Publications and source records attributed to W K Olson.
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Structural details are reported for a novel right-handed polynucleotide double helix stabilized by vertical base stacking and hydrogen bonding. The primary difference between this duplex and the familiar Watson-Crick horizontally stabilized polynucleotide complex arises in the glycosyl rotation of the heterocyclic bases with respect to the sugar-phate backbone. In the vertical double helix the bases adopt a fairly unusual (although not sterically impossible) high-anti conformation, while in the horizontal models deduced from x-ray analyses the bases occur in the favored anti arrangement. The base pairing scheme in both duplexes is the standard Watson-Crick type. The vertical double helix is demonstrated to be a plausible model for the unusual complex formation observed between complementary synthetic polycyclonucleotides (the bases of which are fixed by a chemical linkage in the high-anti orientation) and also a potential alternative ordered structure available to naturally occurring nucleic acid systems that can adopt both anti and high-anti glycosyl arrangements.
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Approximate details of the spatial configuration of the ordered single-stranded poly(rA) molecule in dilute solution have been obtained in a combined theoretical analysis of base stacking and chain flexibility. Only those regularly repeating structures which fulfill the criterion of conformational flexibility (based upon all available experimental and theoretical evidence of preferred bond rotations) and which also exhibit the right-handed base stacking pattern observed in nmr investigations of poly(rA) are deemed suitable single-stranded helices. In addition, the helical geometry of the stacked structures is required to be consistent with the experimentally observed dimensions of both completely ordered and partially ordered poly(rA) chains. Only a single category of poly(rA) helices (very similar in all conformational details to the individual chains of the poly(rA) double-stranded X-ray structure) is thus obtained. Other conformationally feasible polynucleotide helices characterized simply by a parallel and overlapping base stacking arrangement are also discussed.
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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.
A simplified single virtual bond scheme has been developed for the calculation of mean-square unperturbed dimensions in polynucleotide chains. As a consequence of the structural rigidity of the sugar residues in the chain, it is possible to represent the six chemical bonds comprising the chain backbone repeating unit by a single virtual bond (connecting successive phosphorus atoms). The mutual orientation of a pair of adjoining virtual bonds is determined by the angles of rotation about the phosphodiester bonds adjoining intervening phosphorus atoms and is independent of the orientation of all other virtual bonds in the chain. Computed values of chain dimensions based on the single virtual bond scheme are comparable to those calculated previously using a two virtual bond model which permits rotational flexibility in the sugar moieties of the chain.