Department of Biochemistry Box 357350 University of Washington Seattle, WA 98195
 



 
 



               David Baker                      

          Professor of Biochemistry
         Adjunct Professor of Bioengineering
         Adjunct Professor of Genome Sciences 
         Investigator, HHMI

         BA 1984, Harvard University
         PhD 1989, UC Berkeley

         206.543.1295 V
         206.685.1792 F
         dabaker@u.washington.edu
         


Honors

2004 Foresight Institute Feynman Prize
2004 AAAS Newcomb-Cleveland prize
2003 Director, Biomolecular structure and design graduate program (BMSD
2002 International Society for Computational Biology Overton Prize
2000 Protein Society Young Investigator Award
2000 HHMI Assistant Investigator
2000 Editorial Advisory Board, Protein Science
1995 Beckman Young Investigator Award
1994 Packard Fellowship in Science and Engineering
1994 National Science Foundation Young Investigator Award

                                          
Baker Group website          

Research

Our research is focused on the prediction and design of protein structures, protein folding mechanisms, protein-protein interactions, protein-nucleotide interactions, and protein-ligand interactions. Our approach is to use experiments to understand the fundamental principles underlying these problems, to develop simple computational models based on these insights, and to test the models through structure prediction and design. We strive to continually improve our methodology by iterating between computational and experimental studies.

The successful application of our computational prediction and design method, ROSETTA, is illustrated in a few recent examples:

(i) We used computational protein design methods to create an artificial globular protein with a novel fold. Experimentally characterization of Top7 showed that it is extremely stable, and the x-ray crystal structure is strikingly close to the design model. These results suggest that new proteins can be designed with atomic level accuracy, and current work is aimed at using these techniques to design new proteins with novel functions.



Comparisons of the Top7 design (green) and x-ray structure (yellow). (A) C-alpha overlay. (B) Overlay of core sidechains in the C-terminal portion.

(ii) We have redesigned protein-protein interaction specificity and demonstrated that the specificity changes hold both in vitro and in vivo.



7Backbone schematic of the colicin E7 DNase (teal) / Im7 Immunity protein (grey) complex. Important interfacial residues are shown in spacefill (E7 in red, Im7 in blue, conserved Tyr-Tyr motif in yellow).

(iii) Ab initio protein structure prediction. We produced de novo structure predictions of unprecedented accuracy in the recent CASP4 and CASP5 international blind tests of protein structure prediction methods. A more detailed description of our research can be found at http://depts.washington.edu/bakerpg.

Selected Publications

Baker, D. (2000).  A surprising simplicity to protein folding. Nature 405, 39-42.

Kuhlman, B., O'Neill, J. W., Kim, D. E., Zhang, K. Y., Baker, D. (2001).  Conversion of monomeric protein L to an obligate dimer by computational protein design. Proc Natl Acad Sci U S A 98, 10687-91.

Nauli, S., Kuhlman, B., Baker, D. (2001).  Computer-based redesign of a protein folding pathway. Nat Struct Biol 8, 602-5.

Simons, K. T., Strauss, C., Baker, D. (2001).  Prospects for ab initio protein structural genomics. J Mol Biol 306, 1191-9.

Alm, E., Morozov, A., Kortemme, T., Baker, D. (2002).  Simple physical models connect theory and experiment in protein folding kinetics. J Mol Biol 322, 463.

Bonneau, R., Ruczinski, I. , Tsai, J., Baker, D. (2002).  Contact order and ab initio protein structure prediction. Protein Sci 11, 1937-44.

Bonneau, R., Strauss, C., Rohl, C., Chivian, D., Bradley, P., Malmstrom, L., Robertson, T., Baker, D. (2002).  De Novo Prediction of Three-dimensional Structures for Major Protein Families. J Mol Biol 322, 65.

Kortemme, T., Baker, D. (2002).  A simple physical model for binding energy hot spots in protein-protein complexes. Proc Natl Acad Sci U S A 99, 14116-21.

Rohl, C. A., Baker, D. (2002).  De novo determination of protein backbone structure from residual dipolar couplings using Rosetta. J Am Chem Soc 124, 2723-9.

Saunders, C. T., Baker, D. (2002).  Evaluation of structural and evolutionary contributions to deleterious mutation prediction. J Mol Biol 322, 891-901.

Schlosshauer, M., Baker, D. (2002).  A General Expression for Bimolecular Association Rates with Orientational Constraints. J. Phys. Chem. B 106, 12079-12083.

Bradley, P., Chivian, D., Meiler, J., Misura, K. M., Rohl, C., Schief, W., Wedemeyer, W. J., Schueler-Furman, O., Murphy, P., Schonbrun, J., Strauss, C., Baker, D. (2003).  Rosetta predictions in CASP5: Successes, failures, and prospects for complete automation.. Proteins 53, 457-68.

Dantas, G., Kuhlman, B., Callender, D., Wong, M., Baker, D. (2003).  A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins. J Mol Biol 332, 449-60.

Gray, J. J., Moughon, S., Wang, C., Schueler-Furman, O., Kuhlman, B., Rohl, C. A., Baker, D. (2003).  Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol 331, 281-99.

Kortemme, T., Morozov, A. V., Baker, D. (2003).  An orientation-dependent hydrogen bonding potential improves prediction of specificity and structure for proteins and protein-protein complexes. J Mol Biol 326, 1239-59.

Kuhlman, B., Dantas, G., Ireton, G. C., Varani, G., Stoddard, B. L., Baker, D. (2003).  Design of a novel globular protein fold with atomic-level accuracy. Science 302, 1364-8.

Meiler, J., Baker, D. (2003).  Rapid protein fold determination using unassigned NMR data. Proc Natl Acad Sci U S A 100, 15404-15409.

Kuhlman, B., Baker, D. (2004).  Exploring folding free energy landscapes using computational protein design. Current Opinion in Structural Biology 14, 89-95.

Kortemme, T., Joachimiak, L., Bullock, A., Schuler, A., Stoddard, B., Baker D. (2004). Computational redesign of protein-protein interaction specificity. Nature Structural and Molecular Biology 11(4), 371-379.