Abstract

Protein-protein interactions play critical roles in almost all aspects of cellular function and intercellular communication. The proposed research is directed at improving our understanding of the fundamental contributions to the free energy of protein-protein interactions, and using this understanding to redesign protein-protein interaction specificity and to predict the structures of protein-protein complexes from the structures of the unbound partners. The research will involve an integrated combination of computational and experimental approaches. Feedback from the design and prediction studies will guide the development of an improved physical model for the free energy of protein-protein interactions. The design and prediction methods should add significant value to the large number of monomeric protein structures being determined in current large scale structural genomics efforts by allowing them to be assembled into functionally important complexes, and will provide powerful tools for teasing apart complex interaction networks by reprogramming the specificities of individual pairs of interacting proteins. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059224-08
Application #
7324842
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Smith, Ward
Project Start
1999-05-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2009-11-30
Support Year
8
Fiscal Year
2008
Total Cost
$242,404
Indirect Cost

  Institution

Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Karanicolas, John; Corn, Jacob E; Chen, Irwin et al. (2011) A de novo protein binding pair by computational design and directed evolution. Mol Cell 42:250-60
Fleishman, Sarel J; Corn, Jacob E; Strauch, Eva M et al. (2010) Rosetta in CAPRI rounds 13-19. Proteins 78:3212-8
McBeth, Christine; Seamons, Audrey; Pizarro, Juan C et al. (2008) A new twist in TCR diversity revealed by a forbidden alphabeta TCR. J Mol Biol 375:1306-19
Cho, Hyundae D; Sood, Vanita D; Baker, David et al. (2008) On the role of a conserved, potentially helix-breaking residue in the tRNA-binding alpha-helix of archaeal CCA-adding enzymes. RNA 14:1284-9
Korkegian, Aaron; Black, Margaret E; Baker, David et al. (2005) Computational thermostabilization of an enzyme. Science 308:857-60
Chevalier, Brett S; Kortemme, Tanja; Chadsey, Meggen S et al. (2002) Design, activity, and structure of a highly specific artificial endonuclease. Mol Cell 10:895-905