The Crystallization and Structure Analysis of Oligonucleotide Sequences

Until 1976, the study of nucleic acid structure was exclusively the domain of fiber diffractionists. Between the original Watson-Crick structure in 1953 and this date, there was considerable activity in refining the original B-form model of DNA and extending the approach to other polymorphs and a number of synthetic, repetitious polynucleotides, all of which were based on data from fiber-diffraction samples. These studies reached their zenith with the development and use of a “linked-atom,” least-squares refinement procedure for the optimization of mono-or dinucleotide repeat units against the relatively sparse para-crystalline diffraction data from ordered fibers. It is a tribute to the sophistication of these analyses, in spite of the inherent limitations of fiber data, that the refined “canonical” A- and B-DNA double helices are still major reference pomts for many studies (1 ).