Research Interests   Hydrogen exchange in proteins; protein folding; NMR; protein structure, stability and dynamics.

Protein biophysics is the general area of research in our lab. A variety of techniques are employed, including heteronuclear NMR, preparation of protein variants by solid-phase chemical synthesis or by site-directed mutagenesis, differential scanning calorimetry, circular dichroism and fluorescence.

The mechanism of hydrogen isotope exchange in proteins is a long-term interest of our lab. We propose that "the slow exchange core is the folding core" [Woodward, 1993; Kim et al., 1993]. The slow exchange core is a collective term for the elements of packed secondary structure carrying the NHs that are slowest to exchange from the native state by a folded state mechanism. We propose that the sections of peptide chain corresponding to slow exchange core elements are native-like early in folding, when the rest of the protein is more disordered. That is, in the ensemble of interconverting conformations sampled early in folding, the most stable involve native-like interactions between sections that eventually fold into the slow exchange core. Our most recent work involves NMR analysis of partially folded BPTI, prepared by solid phase chemical synthesis in collaboration with Dr. George Barany. Most Recent Work on H-exchange and folding.

In a second project, in collaboration with Dr. Jie Liang and Herbert Edelsbrunner, we have developed a new program, CAST, for identification and measurement of pockets on the surface of proteins [Liang et al., 1998]. The complex shapes of protein surfaces are sculpted by numerous concavities and protrusions which offer unique microenvironments for ligand binding and catalysis. Biologically functional ligands usually employ only one or a few pockets or cavities, those at the active site. CAST employs a computational geometry treatment of complex shapes, based on alpha shape and discrete flow theory of Herbert Edelsbrunner and colleagues. CAST provides a full description of protein pockets and cavities, including volume, surface area, protein atoms that line the concavity, and features of pocket mouth(s) including identification of mouth atoms as well as measurement of mouth area and circumference. The method is completely automatic with no adjustable parameters. Analytical calculation of pocket size is orientationally invariant. One exciting application of CAST is identification of ancillary pockets for 'recruitment' strategies of ligand design. A web server is set up for free CAST calculation of protein pockets and cavities. Web site for CAST.

In a third project, the questions concern the basis for redox activity of the enzymes thioredoxin and glutaredoxin from E. coli. To approach this question, we work in collaboration with Drs. James Fuchs and George Thomas to study unusual titration behavior of the active site residues and the stability and dynamics of both enzymes. See Vohnik et al., 1998 for our most recent work on this subject.

References cited above may be found in the Recent Publications section below.

• Associate Editor, Biochemistry, 2000-2003
• Joint Steering Committee for Public Policy (umbrella committee for biology-related professional societies), member 1999
• President of the Biophysical Society of America, 1997-98.
• Livermore National Labs, Biology Advisory Board, Livermore, CA, 1995-1997
• Los Alamos National Labs, Chemical Science & Technology Division Review Committee, Los Alamos, NM, 1997-2002
• NSF Advisory Panel, Career Awards Program, 1996
• Editorial Board, Folding & Design, 1995-present
• Protein Society Award Selection Committee, 1996
• NSF Advisory Panel, Molecular Biochemistry Program, 1992-1995

• R. F. Cherry National Award for Great Teachers from Baylor University, 1996-97
• Newmark Award Lecture, Univ. of Kansas, Dept. Biochemistry, Lawrence KA, April 1997
• Achievement Award from Minnesota Chapter of Women in Higher Education, 1995
• Morse-Alumni Award for Outstanding Contributions to Undergraduate Education, 1993
• Brasted Teaching Award from Minnesota Chapter of the Am. Chem. Society, 1993

Li, R., & Woodward, C. (1999) "The Hydrogen Exchange Core and Protein Folding." invited review for Protein Science, in press.

Akasaka, K., Li, H., Yamada, H., Li, R., Thoresen, T. & Woodward, C. (1999) "Pressure-induced Amide 15N chemical Shifts in BPTI." in press, Protein Science.

Woodward, C. (1999) "Advances in Protein Hydrogen Exchange from Mass Spectrometry." J. Am. Soc. Mass Spectrom., 10, 672-674.

Woodward, C., & Li, R. (1998) "The Slow Exchange Core and Protein Folding." TIBS, 23, 379.

Liang, Jie, Edelsbrunner, H., & Woodward, C. (1998) "Anatomy of Protein Pockets and Cavities: Measurement of Binding Site Geometry and Implications for Ligand Design." Protein Science, 7, 1884-1897.

Barbar, E., Hare, M., Daragan, V., Barany, G., and Woodward, C. (1998) "Dynamics of the Conformational Ensemble of Partially Folded Bovine Pancreatic Trypsin Inhibitor." Biochemistry,37(21): 7822-7833.

Vohnik, S., Hanson, C., Tuma, R., Fuchs, J., Woodward, C., & Thomas, G. (1998) "Conformation, Stability and Active-Site Cysteine Titrations of the E. coli Mutant D26A Thioredoxin Probed by Raman Spectroscopy." Protein Science, 7, 193-200.

Pan, H., Barany, G., & Woodward, C. (1997) "Reduced BPTI is Collapsed. A Pulsed Field Gradient NMR Study of Unfolded and Partially Folded BPTI." Protein Science, 6, 1-8.

Ilyina, E., Roongta, V., Pan, H., Woodward, C. & Mayo, K. (1997) "A Pulsed Field Gradient NMR Study of BPTI Self-Association." Biochemistry, 36, 3383-3388.

Barbar, E., Gross, C., & Woodward., C., & Barany, G. (1997) "Chemical Synthesis and NMR Characterization of Partially Folded Proteins." Methods in Enzymology, (Academic Press) 289, 587-611.

Barbar, E., Licata, V., Barany, G., & Woodward, C. (1997) "Local Fluctuations and Global Unfolding of Partially Folded BPTI Detected by NMR." Biophysical Chemistry, 64, 45-57. Summary

Barbar, E., Pan, H., Gross, C., Woodward, C., & Barany, G. (1996) "Synthetic and Chemically Modified Models of Bovine Pancreatic Trypsin Inhibitor (BPTI) Folding Intermediates." In Peptides: Chemistry, Structure & Biology. Proceedings of the 14th American Peptide Symposium (P.T.P. Kaumaya and R.S. Hodges, eds.), Mayflower Scientific Ltd., Kingswinford, England, pp 845-846.

Barany, G., Gross, C., Ferrer, M., Barbar, E., Pan, H., & Woodward, C. (1996) "Optimized Methods for Chemical Synthesis of Bovine Pancreatic Trypsin Inhibitor Analogues." In Techniques in Protein Chemistry VII (D. Marshak, ed.), Academic Press, San Diego, pp.503-514.

Barbar, E., Barany, G., & Woodward, C. (1996) "Unfolded BPTI Variants with a Single Disulfide Bond Have Diminished Non-native Structure Distant from the Crosslink." Folding & Design, 1, 65-76. Summary

Pan, H., Barbar, E., Barany, G., & Woodward, C. (1995) "Extensive Non-random Structure in Reduced and Unfolded BPTI." Biochemistry, 34, 13974-13981.

Barbar, E., Barany, G., & Woodward, C. (1995) "Dynamic Structure of a Highly Ordered ß-sheet Molten Globule: Multiple Conformations with a Stable Core." Biochemistry, 34, 11423-11434. Summary

Wilson, N., Barbar, E., Fuchs, J., & Woodward, C. (1995) "Aspartic Acid 26 in Reduced E. coli Thioredoxin Has a pKa >9." Biochemistry, 34, 8931-8939.

Ferrer, M., Barany, G., & Woodward, C. (1995) "Partially Folded, Molten Globule and Molten Coil States of Bovine Pancreatic Trypsin Inhibitor." Nature Structural Biology, 2, 211-217. Summary

Protein Structural Biology in Biomedical Research. Volume 22B in the series "Advances in Molecular & Cell Biology" JAI Press, Greenwich CT, (series ed., E. Bittar; volume eds. N. Allewell & C. Woodward) 1997.