NMR - THIS OTHER METHOD FOR PROTEIN AND NUCLEIC-ACID STRUCTURE DETERMINATION

For a quarter of a century X-ray diffraction in single crystals was un ique in its ability to solve three-dimensional structures of proteins and nucleic acids at atomic resolution. The situation changed in 1984 with the completion of a protein structure determination by nuclear ma gnetic resonance (NMR) spectroscopy in solution, and today NMR is a se cond widely used method for biomacromolecular structure determination. This review describes the method of NMR structure determination of bi ological macromolecules, and attempts to place NMR structure determina tion in perspective with X-ray crystallography. NMR is most powerful f or studies of relatively small systems with molecular weights up to ab out 30 000, but these structures can be obtained in near-physiological milieus. The two techniques have widely different time scales which a fford different insights into internal molecular mobility as well as d ifferent views of protein or nucleic acid molecular surfaces and hydra tion. Generally, in addition to information on the average three-dimen sional structure, NMR provides information on a wide array of short-li ved transient conformational states. Combining information from the tw o methods can yield a more detailed insight into the structural basis of protein and nucleic acid functions, and thus provide a more reliabl e platform for rational drug design and the engineering of novel prote in functions.