Conformational Flexibility of Nucleic Acids

Abstract

In consideration of the importance of conformational flexibility to the functioning of nucleic acids, NMR studies have been carried out to elucidate aspects of dynamics with molecular Mechanics calculations providing supplementary insight. Analysis of 31P and 13C NMR relaxation data in terms of plausible motions in a DNA helix indicate that winding and unwinding, base tilting and base pair propelling are not viable, but sugar repuckering and other limited bond rotations on the nanosecond time scale will account for the data. Molecular mechanics calculations imply that the internal motions are highly localized, not concerted along the length of the DNA helix. 2H and 15N NMR experiments on labeled nucleic acids reveal that the base moieties also eperienci some motions, limited relative to those of the backbone. 31P and 1H NMR studies comparing a closed duplex DNA, pIns36, with linear DNA reveal that segmental motion (apparently bending) occurs two orders of magnitude faster in the cdDNA. The imino proton resonances indicate that there are dynamically-averaged structural differences between linear DNA and supercoiled pIns36 in the A-T base pairs but not the G-C base pairs.