SEQUENCE-SPECIFIC LOCAL STRUCTURAL VARIATIONS IN SOLUTION STRUCTURES OF D(CGXX'CG)(2) AND D(CAXX'TG)(2) SELF-COMPLEMENTARY DEOXYRIBONUCLEICACIDS

In this study, the solution structures of eight self-complementary deo xyribonucleic acid molecules, d(CGXX'CG)(2) and d(CAXX'TG)(2) (where X = C, G, T or A and X' is complementary to X), have been determined us ing NMR interproton distances, endocyclic sugar torsion angles, backbo ne torsion angles and hydrogen bond constraints. Based on the structur al data obtained in solution, a novel sequence-specific local structur e function, Sigma(LS), composed of the sum of the contributions from t he helix twist Omega, base roll rho, base-pair slide Delta delta and p ropeller twist omega, is introduced to describe their sequence-specifi c local structures. Sigma(LS), is found to produce an acceptable corre lation (r = 0.96) with the relative local stability (Delta G(10)(o)) o f a base-pair-step. This result demonstrates that in addition to the i nterstrand purine-purine clashes, the base morphology of nearest-neigh bor base-pairs is also important in defining the local geometry of bas e-pairs. Thus, in analyzing the base-pair structural parameter blocks of trimers are used as the basic unit whereas for the base-pair-step s tructural parameters, the basic unit is composed of blocks of tetramer s. The Sigma(LS)-Delta G(10)(o) correlation is the first experimental evidence demonstrating the relationship between the relative local sta bilities and the sequence-specific local structures of DNA duplexes. I t also forms the basis for using the trimertetramer model for the pred iction of sequence-specific local structures of deoxyribonucleic acid molecules. (C) 1997 Academic Press Limited.