Computational protein design has emerged as a powerful approach for studying the structure and function of proteins. Progress in the field has allowed complex aspects of proteins, included enzymatic activity, to begin to be examined. Design of proteins with enzymatic activity has the potential to provide a new approach to exploring the fundamental mechanisms of enzyme action, and designed enzymes also have numerous possible biotechnology applications. We will use computational methods developed in the DeGrado lab to redesign the active site of a known protein to give it novel catalytic functions. Genetic selections and high-throughput screens will be developed to allow a large number of designed sequences to be analyzed. The resulting designed proteins will be fully characterized structurally and mechanistically in order to evaluate the design process and to compare them to natural enzymes. This information can then be used to improve the designs and the methodology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM073499-03
Application #
7163730
Study Section
Special Emphasis Panel (ZRG1-F04B (20))
Program Officer
Flicker, Paula F
Project Start
2005-01-01
Project End
2007-06-30
Budget Start
2007-01-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$25,214
Indirect Cost
Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Goldberg, Shalom D; Clinthorne, Graham D; Goulian, Mark et al. (2010) Transmembrane polar interactions are required for signaling in the Escherichia coli sensor kinase PhoQ. Proc Natl Acad Sci U S A 107:8141-6
Goldberg, Shalom D; Derr, Paige; DeGrado, William F et al. (2009) Engineered single- and multi-cell chemotaxis pathways in E. coli. Mol Syst Biol 5:283
Goldberg, Shalom D; Soto, Cinque S; Waldburger, Carey D et al. (2008) Determination of the physiological dimer interface of the PhoQ sensor domain. J Mol Biol 379:656-65