The method of choice to reveal the conformation of protein molecules in atomic detail has been X-ray single-crystal analysis. Since the first structural analysis of diffraction patterns, computer calculations have been an important tool in these studies (Blundell & Johnson, 1976). As is described by Sheldrick (1985), it has been taken for granted that a necessary first step in the determination of a protein structure would be writing computer programs to fit structure factors. In contrast the combined use of the structural analysis of NMR data and computer calculations has been quite limited. An early attempt of such structural calculations was the quantitative determination of mononucleotide conformations in solution using lanthanide ion shifts (Barry et al. 1971).

Initial observations of the physical phenomenon of nuclear magnetic resonance (NMR) date back to the late 1940s. In the following two decades high-resolution NMR in solution became an indispensible analytical tool in chemistry, and solid state NMR had an increasingly important role in physics. Some of the potentialities of the method for investigations of complex biological systems had also long been anticipated, and initial experiments with biological specimens were described already 30 years ago. In practice, however, biological applications of NMR have become really attractive only during the last decade, following revolutionary advances in NMR instrumentation and the methodology for their use. NMR projects in biology and medicine now include studies of biomacromolecular structure and function, work on biological membranes, in vivo studies of biochemical processes, and imaging of macroscopic objects. Because of imminent practical applications in medical diagnosis and thanks to extensive coverage by the popular news media, interest in some of the recent developments spreads far beyond the scientific community, making NMR a widely popular field.

The three-dimensional structures of proteins are among the most valuable contributions of biophysics to the understanding of biological systems (Dickerson & Geis, 1969; Creighton, 1983). Protein structures are utilized in the description and interpretation of a wide variety of biological phenomena, including genetic regulation, enzyme mechanisms, antibody recognition, cellular energetics, and macroscopic mechanical and structural properties of molecular assemblies. Virtually all of the information currently available about the structures of proteins at atomic resolution has been obtained from diffraction studies of single crystals of proteins (Wyckoff et al, 1985). However, recently developed NMR methods are capable of determining the structures of proteins and are now being applied to a variety of systems, including proteins in solution and other non-crystalline environments that are not amenable for X-ray diffraction studies. Solid-state NMR methods are useful for proteins that undergo limited overall reorientation by virtue of their being in the crystalline solid state or integral parts of supramolecular structures that do not reorient rapidly in solution. For reviews of applications of solid-state NMR spectroscopy to biological systems see Torchia and VanderHart (1979), Griffin (1981), Oldfield et al. (1982), Opella (1982), Torchia (1982), Gauesh (1984), Torchia (1984) and Opella (1986). This review describes how solid-state NMR can be used to obtain structural information about proteins. Methods applicable to samples with macroscopic orientation are emphasized.

An exciting aspect of NMR spectroscopy is its ability to monitor, non-invasively, a variety of small molecules in cells and tissues. This leads to the possibility of investigating details of cellular biochemistry previously obscured by separation and purification procedures.

A survey of magnetic resonance imaging techniques is presented. Emphasis is put on the basic types of measurement procedures rather than, discussing all variants proposed so far. The general experimental procedure consists of two phases, the preconditioning period and the image formation period. While the preconditioning period determines the image contrast, the image formation process is responsible for image resolution. Means to improve sensitivity and to minimize measurement time are discussed.

The proton has been the nucleus of choice for NMR studies of macromolecules because it is ubiquitous; it provides the highest sensitivity; its resonances can be identified with types of amino and nucleic acids by means of experiments utilizing proton spin-spin interaction and chemical shift; and, most important, proton NMR yields distance information via the nuclear Overhauser effect (NOE). Many of these advantages are lost for larger biopolymers (molecular weight more than 15 kDa) for which the line width is considerably greater than the proton-proton spin-spin interaction. The spin-spin interaction is then useless or difficult to use for assignment; and furthermore the proton line width and the number of proton resonances both increase in proportion to the molecular weight, thereby increasing the problem of resonance overlap to an intolerable degree.

Biological systems must have evolved in an interplay between a great many organic and inorganic compounds. As a result a considerable number of elements - estimates range between 25 and 30 - are essential for higher life forms such as animals and man (Underwood, 1977; Williams, 1983, 1984).

In the very short time since magnetic resonance imaging (MRI) was born it has gained surprisingly rapid and enthusiastic acceptance and has speedily proliferated, particularly in the United States and Western Europe. Magnetic resonance imaging (MRI) has successfully challenged computed tomography (CT) in all areas of the body where respiratory motion does not degrade the image (Steinberg, 1986). Newer techniques using a multiplicity of approaches are starting to close the gap between CT and MRI, even in the upper abdomen where the effects of respiratory motion are most pronounced. Although MR is already widely clinically applied and is an accepted everyday diagnostic modality in most large medical centres in the United States, it is not a mature modality. It is rapidly evolving, with whole new areas opening to investigation which will vastly broaden its applications.