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Robert G. Griffin
Director, Francis Bitter Magnet Laboratory/ Professor of Chemistry

A large fraction of our research effort is devoted to the development of new magnetic resonance techniques to study molecular structure and dynamics. Typical of the problems that we address is the design of experiments to measure 13C-13C and 13C-15N dipolar couplings, and therefore to perform spectral assignments and to measure internuclear distances and torsion angles, in solids from magic angle spinning (MAS) NMR spectra. This information leads directly to molecular structures of amyloid and membrane peptides and proteins (vide infra). In addition, we are developing high field dynamic nuclear polarization (DNP)/NMR experiments. The motivation behind this research is the possibility to obtain large nuclear spin polarizations, and therefore increased NMR signal intensities. The top figure at the left illustrates signal enhancements recorded from a sample of U(13C,15N) proline where we have observed a factor of ~20 larger signal strengths when the sample is doped with paramagnetic centers and irradiated with 250 GHz microwaves. The experiments have developed to the point where it is possible to record multiple dimensional spectra as illustrated in the middle panels of the figure. This increased signal intensities should enable many new applications to be addressed. As part of this project, we are also performing CW and pulsed EPR experiments at 140 GHz. For systems not susceptible to g-strain, the higher EPR frequencies offer considerably increased resolution and ease of interpretation of the spectral lineshapes. Finally, we are also involved in the development of approaches for investigating dynamic processes in solids. Generally, these experiments involve analysis of 2H NMR powder patterns, and details concerning the rates and mechanism of the motion are derived from the lineshapes.

The second major part of our research is the application of the magnetic resonance techniques described above to interesting chemical, biophysical, and physical problems. We are currently employing MAS NMR experiments to investigate the structure of large enzyme/inhibitor complexes, membrane proteins and amyloid peptide and proteins. By measuring chemical shifts and dipolar couplings between homonuclear and heteronuclear spin pairs in inhibitors or active sites, we have been able to address structural questions in several cases. For example, we have performed NMR on photochemical intermediates of bacteriorhodopsin trapped at low temperature to study the mechanism of proton pumping and the origin of the opsin shift in the optical spectrum of retinal in this protein. More recently we have completed the initial two structures of peptides with MAS dipole recoupling techniques. One of these, an 11-mer from the protein transthyretin, is illustrated in the bottom part of the figure and is the initial structure of a peptide in an amyloid fibril. Since these molecules do not diffract and are not soluble, their structures can only be determined by high resolution solid state NMR.

C.T. Farrar, D.A. Hall, G.J. Gerfen, S.J. Inati and R.G. Griffin, “Mechanism of Dynamic Nuclear Polarization in High Magnetic Fields,” J. Chem. Physics 114, 4922 – 4933 (2001)
G. Bar, M. Bennati, H.T. Nguyen, J. Ge, J. Stubbe, R.G. Griffin, “High Frequency (140 GHz) Time Domain EPR and ENDOR Spectroscopy: The Tyrosyl Radical-Diiron Cofactor in Ribonucleotide Reductase from Yeast,” J. Am. Chem. Soc. 123, 3569-3576 (2001)
M.Bennati, J. Stubbe, and R.G. Griffin, High Frequency EPR and ENDOR: Time Domain Spectroscopy of Ribonucleotide Reductase,” Applied Magnetic Resonance 21 389-410 (2001)
C.P. Jaroniec, J Lansing, B. Tounge, M. Belenky, J. Herzfeld, and R.G. Griffin, “Measurement of Dipolar Couplings In a Uniformly 13C/15N Labeled Membrane Protein: Distances between the Schiff Base and Aspartic Acids in the Active site of Bacteriorhodopsin” J. Am. Chem. Soc. 123, 12,929-12,930 (2001)
C. M. Rienstra, M. Hohwy, L. J. Mueller, C. P. Jaroniec, B. Reif, R. G. Griffin "Determination of multiple torsion-angle constraints in U-13C,15N-labeled peptides: 3D 1H-15N-13C-1H dipolar chemical shift spectroscopy in rotating solids,", J. Am. Chem. Soc. 124, 11908-11922 (2002)
M. Rosay, V. Weis, K.E. Kreischer, R.J. Temkin, and R. G. Griffin, “Two-Dimensional 13C-13C Correlation Spectroscopy with Magic Angle Spinning and Dynamic Nuclear Polarization”, J. Am. Chem. Soc. 124, 3214-3215 (2002)
C.M. Rienstra, L. Tucker-Kellogg, C.P. Jaroniec, M. Hohwy, B. Reif, T. Lozano-Peres, B.Tidor, and R,G, Griffin, “De Novo Structure Determination of Peptides and Proteins with High Resolution Solid State MAS NMR” Proc. National Academy of Science 99, 10260-10265 (2002)
C. P. Jaroniec, C. Filip and R G. Griffin, “3D TEDOR NMR Experiments for the Simultaneous Measurement of Multiple Carbon-Nitrogen Distances in Uniformly 13C,15N-Labeled Solids,” J. Am. Chem. Soc. 124, 10728-10742 (2002)
C.P. Jaroniec, C.E. MacPhee, N.S. Astrof, C.M. Dobson, R.G. Griffin, “Molecular Conformation of a Peptide Fragment of Transthyretin in an Amyloid Fibril, Proc. National Academy of Science 99, 16748-16753 (2002)
V.S. Bajaj, C.T. Farrar, M.K. Hornstein, I. Mastovsky, J. Bryant, K.E. Kreischer, R.J. Temkin, and R.G. Griffin, ”Dynamic Nuclear Polarization at 9 Tesla Using a Novel 250 GHz Gyrotron Microwave Source,” J. Magn. Resonance 160, 85-90 (2003)

Contact Information

Francis Bitter Magnet Laboratory
166 Albany Street, NW14-5113
Cambridge, MA 02139

Phon: 617-253-5597
Fax: 617-253-5405
Email: rgg@mit.edu

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Griffin Group

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Francis Bitter Magnet Laboratory
NW14, 150 Albany Street
Cambridge, MA 02139
Phone: (617) 253-5478
Email: jhaggert@mit.edu