Early Strides in NMR Dynamics Measurements.

The study of protein dynamics using the measurement of relaxation times by NMR was based on a set of studies in the mid-20th century that outlined theories and methods. However, the complexity of protein NMR was such that these simple experiments were not practical for application to proteins. The advent of techniques in the 1980s for isotopic labeling of proteins meant that pulse sequences could now be applied in multidimensional NMR experiments to enable per-residue information about the local relaxation times. One of the earliest advances was published in Biochemistry in 1989. The paper "Backbone dynamics of proteins as studied by 15N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease" by Lewis Kay, Dennis Torchia, and Ad Bax delineated a set of pulse sequences that are used with minor modifications even today. This paper, with others from a limited number of other laboratories, forms the basis for the experimental determination of the backbone dynamics of proteins. The biological insights obtained from such measurements have only increased in the past 30 years. Sometimes, the best and perhaps only way to advance a field is an advancement in the technical capabilities that allows new perspectives to be reached.

Biomolecular NMR: Past and future.

The editors of this special volume suggested this topic, presumably because of the perspective lent by our combined >90-year association with biomolecular NMR. What follows is our personal experience with the evolution of the field, which we hope will illustrate the trajectory of change over the years. As for the future, one can confidently predict that it will involve unexpected advances. Our narrative is colored by our experience in using the NMR Facility for Biomedical Studies at Carnegie-Mellon University (Pittsburgh) and in developing similar facilities at Purdue (1977-1984) and the University of Wisconsin-Madison (1984-). We have enjoyed developing NMR technology and making it available to collaborators and users of these facilities. Our group's association with the Biological Magnetic Resonance data Bank (BMRB) and with the Worldwide Protein Data Bank (wwPDB) has also been rewarding. Of course, many groups contributed to the early growth and development of biomolecular NMR, and our brief personal account certainly omits many important milestones.

The quiet renaissance of protein nuclear magnetic resonance.

From roughly 1985 through the start of the new millennium, the cutting edge of solution protein nuclear magnetic resonance (NMR) spectroscopy was to a significant extent driven by the aspiration to determine structures. Here we survey recent advances in protein NMR that herald a renaissance in which a number of its most important applications reflect the broad problem-solving capability displayed by this method during its classical era during the 1970s and early 1980s.

Is biomedical nuclear magnetic resonance limited by a revisitable paradigm in physics?

The history of nuclear magnetic resonance (NMR) can be divided generally into two phases: before the Second World War, molecular beam methods made it possible to detect the whole set of spins. However, these methods were destructive for the sample and had a very low precision. The publications of F. Bloch and E. Purcell in 1946 opened up a second phase for NMR with the study of condensed matter, but at the expense of an enormous loss in theoretical sensitivity. During more than half a century, the method of Bloch and Purcell, based on inductive detection of the NMR signal, has allowed many developments in biomedicine. But, curiously, this severely constraining limitation on sensitivity has not been called into question during this half-century, as if the pioneers of the pre-war period had been forgotten.