Incorporating residual dipolar couplings into the NMR solution structure determination of nucleic acids.

Abstract

NMR solution structures of nucleic acids are generally less well defined than similar-sized proteins. Most NMR structures of nucleic acids are defined only by short-range interactions, such as intrabase-pair or sequential nuclear Overhauser effects (NOEs), and J-coupling constants, and there are no long-range structural data on the tertiary structure. Residual dipolar couplings represent an extremely valuable source of distance and angle information for macromolecules but they average to zero in isotropic solutions. With the recent advent of general methods for partial alignment of macromolecules in solution, residual dipolar couplings are rapidly becoming indispensable constraints for solution NMR structural studies. These residual dipolar couplings give long-range global structural information and thus complement the strictly local structural data obtained from standard NOE and torsion angle constraints. Such global structural data are especially important in nucleic acids due to the more elongated, less-globular structure of many DNAs and RNAs. Here we review recent progress in application of residual dipolar couplings to structural studies of nucleic acids. We also present results showing how refinement procedures affect the final solution structures of nucleic acids.