Base sequence effects in double‐helical DNA. III. Average properties of curved dna

The matrix‐generator methods set forth in the preceding paper for treating rodlike DNA are adapted here to the calculation of average chain extension, macroscopic flexibility, and terminal residue orientation in curved duplexes. The different characteristics of curved vs rodlike chains are illustrated with the hypothetical poly[d(A 5 G 5 )] · poly[d(T 5 C 5 )] duplex. The curved helix is both more compact and macroscopically stiffer than either the poly(dA) · poly(dT) or the poly(dG) · poly(dC) chain. The calculations have also been extended to simple repetitive DNA sequences generated by synthetic ligation studies and the computed average chain properties compared with observed gel mobilities. The predicted chain extension is also checked against the measured persistence lengths of the rodlike poly[d(GC)] and poly[d(AT)] alternating copolymers, and the known cyclization tendencies of selected repeating sequences. Chains are generated from local potential energy maps describing the morphology and flexibility of adjacent base pairs. The energy maps, while approximate, are more accurate descriptors of local structure than many of the intuitive models of DNA curvature offered to date. According to the energy surfaces, the intrinsic bending of curved DNA can be traced to asymmetry in the bending of the Gs and Cs that join half‐helical turn stretches of adenines in these chains. The oligo A stretches are analogous to residues of a perfectly elastic DNA that bend with equal likelihood in opposing directions. In other models of DNA curvature, the (G · C) base pairs are presumed to adopt the classical B‐DNA structure, while the (A · T) base pairs are thought to be in some perturbed conformation.