Resolving the discrepancies among nucleic acid conformational analyses

Growing interest in understanding the relationship between the global foldi ng of nucleic acids and the sequence-dependent structure of individual base -pair steps has stimulated the development of new mathematical methods to d efine the geometry of the constituent base-pairs. Several approaches, desig ned to meet guidelines set by the nucleic acid community, permit rigorous c omparative analyses of different three-dimensional structures, as well as a llow for reconstruction of chain molecules at the base-pair level. The diff erent computer programs, however, yield inconsistent descriptions of chain conformation. Here we report our own implementation of seven algorithms use d to determine base-pair and dimer step parameters. Aside from reproducing the results of individual programs, we uncover the reasons why the differen t algorithms come to conflicting structural interpretations. The choice of mathematics has only a limited effect on the computed parameters, even in h ighly deformed duplexes. The results are much more sensitive to the choice of reference frame. The disparate schemes yield very similar conformational descriptions if the calculations are based on a common reference frame. Th e current positioning of reference frames at the inner and outer edges of c omplementary bases exaggerates the rise at distorted dimer steps, and point s to the need for a carefully defined conformational standard. (C) 1999 Aca demic Press.