William F. DeGrado

faculty photo
Adjunct Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
1009 Stellar-Chance Laboratories
422 Curie Boulevard
Philadelphia, PA 19104
Office: (215) 898-4590
Fax: (215) 573-7229
Education:
(Chemistry)
Northcentral College , 1975.
B.S.
Kalamazoo College, 1977.
Ph.D. (Chemistry)
University of Chicago, 1981.
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Description of Research Expertise

Our group's research focuses on protein design as an approach to understanding macromolecule structure and function. Our primary research interest is in the de novo design, in which one designs proteins beginning from first principles. This approach critically tests our understanding of protein folding and function, while also laying the groundwork for the design of proteins and biomimetic polymers with properties unprecedented in nature. The de novo design of proteins has proven to be a useful approach for understanding the features in a protein sequence that cause them to fold into their unique three-dimensional structures. In addition, it has been possible to design functionally interesting proteins, which bind redox-active cofactors, DNA, and transition metals. Finally, this approach has been extended to the design of membrane-active proteins, including ion channels, antibiotics and fusogenic agents.

Description of Itmat Expertise

Dr. DeGrado utilizes de novo design of proteins (designing proteins from first principals) to critically test protein folding and function. Studies include the design of small molecules that inhibit the interaction of cells with the extracellular matrix by binding to a class of membrane proteins known as integrins and the structure and function of membrane-active peptides.

Selected Publications

Gratkowski, H., Dai, Q.H., Wand, A.J., DeGrado, W.F. & Lear, J.D. : "Cooperativity and specificity of association of a designed transmembrane peptide" Biophys J 83: 1613-1619, 2002.

Howard, K.P., Lear, J.D. & DeGrado, W.F. : "Sequence determinants of the energetics of folding of a transmembrane four-helix-bundle protein" Proc Natl Acad Sci USA 99: 8568-8572, 2002.

Huang, C.Y., He, S., DeGrado, W.F., McCafferty, D.G. & Gai, F. : "Light-induced helix formation" J Am Chem Soc 124: 12674-12675, 2002.

Ghirlanda, G., Lear, J.D., Ogihara, N.L., Eisenberg, D. & DeGrado, W.F. : "A hierarchic approach to the design of hexameric helical barrels" J Mol Biol 319: 243-253, 2002.

Marsh, E. N. G., DeGrado, W. F. : "Noncovalent self-assembly of a heterotetrameric diiron protein" Proc. Natl. Acad. Sci. USA 99: 5150-5154, 2002.

Huang, C. Y., Getahun, Z., Zhu, Y., Klemke, J. W., DeGrado, W. F. & Gai, F. : "Helix formation via conformation diffusion search" Proc Natl Acad Sci USA 99: 2788-2793, 2002.

Cheng, R.P. & DeGrado, W.F. : "Long-range interactions stabilize the fold of a non-natural oligomer" J Am Chem Soc 124: 11564-11565, 2002.

Summa, C.M., Rosenblatt, M.M., Hong, J.K., Lear, J.D. & DeGrado, W.F. : "Computational de novo design, and characterization of an A(2)B(2) diiron protein" J Mol Biol 321: 923-938, 2002.

Xue, C.-B.; Voss, M. E.; Nelson, D. J.; Duan, J.-W.; Cherney, R. J.; Jacobson, I. C.; He, X.; Roderick, J.; Chen, L.; Corbett, R. L.; Wang, L.; Meyer, D. T.; Kennedy, K.; DeGrado, W. F.; Hardman, K. D.; Teleha, C. A.; Jaffee, B. D.; Liu, R.-Q.; Copeland, R. A.; Covington, M. B.; Christ, D. D.; Trzaskos, James M.; Newton, R. C.; Magolda, R. L.; Wexler, R. R.; Decicco, C. P. : "Design, Synthesis, and Structure-Activity Relationships of Macrocyclic Hydroxamic Acids That Inhibit Tumor Necrosis Factor a Release in Vitro and in Vivo" J. Med. Chem. 44(16): 2636-2660, 2001.

Lear, J. D., Gratkowski, H., DeGrado, W. F. : “De novo design, synthesis, and characterization of membrane-active peptides” Biochem. Soc. Transactions 29: 559-564, 2001.

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Last updated: 10/04/2011
The Trustees of the University of Pennsylvania