The overall goal of our laboratory is to characterize the structure/function relationships of a variety of enzymatic catalysts at the atomic level. Much of this work is being extended into efforts to engineer novel properties onto existing enzyme scaffolds. Most of our particular area of focus is on enzymes that act to modify nucleic acid substrates, and a unifying theme between many of the individual projects is the selection and engineering of these enzymes for targeted therapeutic applications.
The tools employed by our lab are X-ray crystallography, computer modeling, and genetic manipulation of the molecules of interest, combined with biochemical analyses of function.
"Crystallographic analyses illustrate significant plasticity and efficient recoding of meganuclease target specificity" Werther, R., Hallinan, J. P., Lambert, A., Jarjour, J., Havens, K, Galizi, R., Windbichler, N., Crisanti, A., Nolan, T. and Stoddard, B.L.
“De novo design of a fluorescence-activating beta-barrel” Dou, J., Vorobieva, A., Sheffler, W., Doyle, L., Park, H., Bick, M. J., Mao, B., Foight, G. W., Lee, M. Y., Carter, L., Sankaran, B., Ovchinnikov, S., Marcos, E., Huang, P. -S., Vaughan, J. C., Stoddard, B. L. and Baker, D.