Patricia Babbitt

Research Interests

Computational biology/bioinformatics research for inference of function, understanding protein structure-function; experimental enzyme design

Research Summary

We are studying protein structure-function relationships viewed from the perspective of evolutionarily related proteins in superfamilies. The idea is that by understanding how nature has re-engineered a given protein scaffold for a variety of functions, we gain insight about the fundamental rules by which protein structure mediates function. These computational analyses have led to new models for enzyme evolution, thereby providing a conceptual framework for inference of functional capabilities from structural information. This work has been successfully applied to such problems as the prediction of function for unknown reading frames and to provide guidance for experimental protein engineering. The wet bench side of the lab focuses on testing these models using both rational design and combinatorial approaches to generate proteins with specific new functions.

Selected Publications

Glasner ME, Fayazmanesh N, Chiang RA, Sakai A, Jacobson MP, Gerlt JA, Babbitt PC. Evolution of Structure and Function in the o-Succinylbenzoate Synthase/N-Acylamino Acid Racemase Family of the Enolase Superfamily. J Mol Biol., 2006.

Pegg, S.C.-H., Brown, S.D., Ojha, S., Seffernick, J., Meng, E.C., Morris, J.H., Chang, P.J., Huang, C.C. Ferrin, T.E. & Babbitt, P.C. Leveraging enzyme structure-function relationships for functional inference & experimental design: The structure-function linkage database. Biochem., 2006. 

Polacco, B.J. & Babbitt, P.C. Automated discovery of 3D motifs for protein function information. Bioinf., 2006.

Copley, S.D., Novak, W.R.P. & Babbitt, P.C. Divergence of function in the thioredoxin-fold suprafamily: Evidence for evolution of peroxiredoxins from a thioredoxin-like ancestor. Biochem., 2004. 

Schmidt, D.M.Z., Mundorff, E.C., Dojka, M., Bermudez, E., Ness, J.E., Govindarajan, S., Babbitt, P.C., Minshull, J., & Gerlt, J.A. Evolutionary potential of beta-alpha(8) Barrels: Functional promiscuity produced by single substitutions in the enolase superfamily. Biochem., 2003.