title: The importance of being ordered: improving NMR structures using residual dipolar couplings.
abstract: Residual dipolar couplings arise from small degrees of alignment of molecules in a magnetic field. Most biomolecules lack sufficient intrinsic magnetic susceptibility anisotropies for practical purposes; however, alignment can be achieved using dilute aqueous phospholipid mixtures, colloidal suspensions of rod-shaped viruses, complex phases of surfactant systems and strained gels. The stability of the liquid crystalline phases varies with respect to temperature range, pH variation and time and is critically dependent on sample composition and experimental conditions. The magnitude of the residual dipolar couplings depends upon the degree of ordering and allows the determination of the corresponding inter-nuclear vectors with respect to the molecule's alignment frame. Inclusion of dipolar constraints into NMR structure calculations leads to improved precision and accuracy of the resulting structures, especially in cases where the information content provided by traditional NOE constraints is limited. In addition, rapid evaluation of backbone protein folds and determination of the relative orientations of individual components in multi-molecular complexes have become feasible. Dipolar coupling based strategies may well emerge as the most critical developments, in establishing NMR as a valuable and competitive methodology in the structural genomics initiative.
authors.affiliation: Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. gronenborn@nih.gov
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D001435:Bacteriophages / Q000648:ultrastructure; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003102:Colloids; D003460:Crystallization; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D005782:Gels; D008280:Magnetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010742:Phospholipid Ethers / Q000737:chemistry; D017510:Protein Folding; D013501:Surface-Active Agents / Q000737:chemistry; D014027:Tobacco Mosaic Virus / Q000648:ultrastructure
chemical_list: C052298:1,2-dihexadecyl-sn-glycero-3-phosphocholine; D003102:Colloids; D005782:Gels; D010742:Phospholipid Ethers; D013501:Surface-Active Agents; D004134:Dimyristoylphosphatidylcholine