Sloan Research Fellowship (2014) Appointed to UC Davis faculty (2012) Senior Fellow, University of Washington, Seattle (2012) Ph.D. University of Washington, Seattle (2011) B.S. UC Davis (2005)

Computational Enzyme Design My scientific efforts are focused on combining computational and experimental tools to develop a fundamental knowledge of enzyme catalysis, and applying those principles to design novel proteins of therapeutic or commercial interest. Currently I am working with an international community on the development of Rosetta computational methodology for predicting and designing macromolecular structures, interactions, and functions. Using this methodology I have completed the de novo design of enzymes capable of catalyzing chemical reactions not found in nature, such as the Diels-Alder reaction. This was followed up by working with an online community, Foldit, to further engineer these proteins for enhanced activity. Most recently I have worked on the redesign of naturally occurring enzymes for the degradation of immunogenic gluten proteins, to develop a novel CO2 fixation pathways, and design of a novel anthrax therapeutic. My current focus is on the design of novel biofuel and commodity chemical biosynthetic pathways, the development of novel therapeutics, and the general understanding of the relationship between protein sequence, structure, and function.

My scientific efforts are focused on combining computational and experimental tools to develop a fundamental knowledge of enzyme catalysis, and applying those principles to design novel proteins of therapeutic or commercial interest. Currently I am working with an international community on the development of Rosetta computational methodology for predicting and designing macromolecular structures, interactions, and functions. Using this methodology I have completed the de novo design of enzymes capable of catalyzing chemical reactions not found in nature, such as the Diels-Alder reaction. This was followed up by working with an online community, Foldit, to further engineer these proteins for enhanced activity. Most recently I have worked on the redesign of naturally occurring enzymes for the degradation of immunogenic gluten proteins, to develop a novel CO2 fixation pathways, and design of a novel anthrax therapeutic. My current focus is on the design of novel biofuel and commodity chemical biosynthetic pathways, the development of novel therapeutics, and the general understanding of the relationship between protein sequence, structure, and function.

Siegel, J. B., Zanghellini A., Lovick H. M., Kiss G., Lambert A. R., St Clair J. L., Gallaher J. L., Hilvert D., Gelb M. H., Stoddard B. L., Houk K. N., Michael F. E., & Baker D. Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction. Science. 2010;329(5989):309-13. DOI: 10.1126/science.1190239 Wu S.J., Eiben C.B., Carra J.H., Huang I., Zong D., Liu P., Wu C., Nivala J., Dunbar J., Huber T., Senft J., Schokman R., Smith M.D., Mills J.H, Friedlander A.M., Baker D., Siegel J.B. Improvement of a potential anthrax therapeutic by computational protein design. JBC 2011: 286: 32586-32592. DOI: 10.1074/jbc.M111.251041

Siegel J.B.*, Eiben C.B.*, Bale J., Foldit Players, Khatib F., Cooper S., Shen B.W., Stoddard B.L., Popovic Z., Baker D. Increased Diels-Alderase activity through FoldIt player guided backbone remodeling. Nature Biotechnology 2012: 30: 190-192 DOI: 10.1038/nbt.2109