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

 2007 Editorial Board, PNAS
2006 National Academy of Sciences
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

Rothlisberger D, Khersonsky O, Wollacott AM, Jiang L, Dechancie J, Betker J, Baker, D. Kemp elimination catalysts by computational enzyme design. Nature 2008 May 8; 453, 190-195.

Jiang L, Althoff EA, Clemente FR, Doyle L, Rothlisberger D, Zanghellini A, Baker, D. De novo computational design of retro-aldol enzymes. Science 2008 Mar 7;319(5868):1387-91.

Watters AL, Deka P, Corrent C, Callender D, Varani G, Sosnick T, et al. The highly cooperative folding of small naturally occurring proteins is likely the result of natural selection. Cell. 2007 Feb;128(3):613-24.

Qian B, Raman S, Das R, Bradley P, McCoy AJ, Read RJ, et al. High-resolution structure prediction and the crystallographic phase problem. Nature. 2007 Nov;450(7167):259-U7.

Barth P, Schonbrun J, Baker D. Toward high-resolution prediction and design of transmembrane helical protein structures. Proceedings of the National Academy of Sciences of the United States of America. 2007 Dec 18;104(51):20635.

Das R, Baker D. Automated de novo prediction of native-like RNA tertiary structures. Proceedings of the National Academy of Sciences of the United States of America. 2007 Sep;104(37):14664-9.

Malmstrom L, Riffle M, Strauss CEM, Chivian D, Davis TN, Bonneau R, Baker, D. Superfamily assignments for the yeast proteome through integration of structure prediction with the gene ontology. Plos Biology. 2007 Apr;5(4):758-68.

Ashworth J, Havranek JJ, Duarte CM, Sussman D, Monnat RJ, Jr., Stoddard BL, Baker, D. Computational redesign of endonuclease DNA binding and cleavage specificity. Nature 2006 Jun 1;441(7093):656-9.

Bradley P, Misura KM, Baker D. Toward high-resolution de novo structure prediction for small proteins. Science 2005 Sep 16;309(5742):1868-71.

Schueler-Furman O, Wang C, Bradley P, Misura K, Baker D. Progress in modeling of protein structures and interactions. Science 2005 Oct 28;310(5748):638-42

Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D. Design of a novel globular protein fold with atomic-level accuracy. Science. 2003 Nov;302(5649):1364-8.