David Baker, PhD, Director of the Institute for Protein Design
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. Experimental 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.
Backbone 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.
David Baker is Professor of Biochemistry, Director of the Institute for Protein Design, Investigator of the Howard Hughes Medical Institute, and adjunct professor of Genome Sciences, Bioengineering, Chemical Engineering, Computer Science, and Physics at the University of Washington. He received his Ph.D. degree in biochemistry with Randy Schekman at the University of California, Berkeley and did postdoctoral work in biophysics with David Agard at UCSF. His research group is focused on the prediction and design of macromolecular structures, interactions and functions. Dr. Baker received young investigator awards from the National Science Foundation and the Beckman Foundation, and the Packard Foundation fellowship in Science and Engineering. He has also received the Irving Sigal Young Investigator award from the Protein Society and the Overton Prize from the International Society of Computational Biology. He is a recipient of the Feynman Prize from the Foresight Institute, the AAAS Newcomb_Cleveland prize, the Sackler prize in biophysics, and the Centenary award from the Biochemical society. He is a member of the National Academy of Sciences and the American Academy of Sciences. His research group is a world leader in computational protein design and protein structure prediction.
1994 National Science Foundation Young Investigator Award
1994 Packard Fellowship in Science and Engineering
1995 Beckman Young Investigator Award
1999 Nominating Committee, Protein Society
2000 Editorial Advisory Board, Protein Science
2000 HHMI Assistant Investigator
2000 Protein Society Young Investigator Award
2002 International Society for Computational Biology Overton Prize
2003 Director, Biomolecular structure and design graduate program (BMSD)
2004 AAAS Newcomb-Cleveland prize
2004 Foresight Institute Feynman Prize
2006 National Academy of Sciences
2007 Editorial Board, PNAS
2008 Sackler Prize in Biophysics
2009 American Academy of Sciences
2011 University of Washington Inventor of the Year Award
2012 Biochemical Society Centenary Award
2014 David Perlman Memorial Award