Biomolecular NMR: Past and future

Abstract

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.

Keywords: Biomolecular NMR history; Computational approaches; NMR instrumentation; Pulse sequence development; Sample preparation and labeling.

Fig. 1

Biomolecular NMR group at the Merck Institute, Rahway, New Jersey, in 1967. From left to right: Donella Meadows, Oleg Jardetzky, Jack Cohen, and John Markley. Jack Cohen had a long research career at the NIH and later in Israel. Donella Meadows left NMR after her PhD to become a pioneering environmental scientist, teacher, and writer. She is best known as the lead author of The Limits to Growth and Thinking in Systems: a Primer. She was a Pew Scholar in Conservation and Environment and a MacArthur Fellow. Photograph from Business Week, December 2, 1967, page 94; reprinted with permission.

Fig. 2

Varian HR-220 (220 MHz) NMR spectrometer and console, Calcomp 565 chart recorder, home-built pulse gear, PDP-11 computer, and magnetic tape recorder in Mel Klein’s laboratory at UC Berkeley. Bill Horsely, who worked with John Markley, is sitting at the NMR spectrometer. Reproduced from “Chemical Biodynamics Group,” Lawrence Radiation Laboratory, University of California, Berkeley, California, USAEC Pub. No. 33, September 1970, p. 6.

Fig. 3

Milo Westler and Nicolet NT-1180 computer and console at PUBMRL in 1979. Photo taken by JLM.

Fig. 4

Brian Stockman observing a quench during the installation of the Bruker 600 at NMRFAM in 1988. Photo taken by JLM.

Fig. 5

Delivery of the Varian 900 MHz NMR spectrometer at NMRFAM in 2003. The facility was designed with a hatch in the ceiling to accommodate large pieces of equipment. Photo taken by JLM.

Fig. 6

NMRFAM spectrometers (plot of field strength vs. delivery date).

Fig. 7

Array processor used for early processing of 3D NMR data at NMRFAM. Photo taken by WMW.

Fig. 8

High frequency region of 100 MHz ¹H NMR spectra of (a) unlabeled staphylococcal nuclease and (b) selectively-deuterated staphylococcal nuclease. From publication [98]. Tryptophan was added to the growth medium containing deuterated amino acids. Signals from histidine and tyrosine were present because of back exchange during HCl hydrolysis of the deuterated algal protein that was the source of the deuterated amino acids. Reprinted from Fig. 1, Proc. Natl. Acad. Sci. U.S.A. 64:1399 (1969).

Fig. 9

Comparison of the 100 MHz NMR spectra of the histidine ring proton regions of staphylococcal nuclease (Nase) isolated from the Foggi (a) and (c) and V8 (b) and (d) strains of Staphylococcus aureus [68]. Because amino acid sequencing showed that residue 174 in Nase from the Foggi strain is histidine whereas it is leucine in Nase from the V8 strain [21], the spectra enable peak H3 to be assigned to H124. Reprinted from John Markley’s Ph.D. thesis, p. 165.