Education
1978 Ph.D., Northwestern University
1974 B.A., Reed College

Honors and Awards
1987 Alfred P. Sloan Foundation Fellowship
1989 Excellence in Teaching Award
1997 Sequoyah Fellow, American Indian Science and Engineering Society

Research Interests
The group of Prof. Ondrechen works in the areas of theoretical and computational chemistry and chemical biology. Areas of interest include functional genomics - prediction of the functional roles of gene products (proteins), modeling of enzyme-substrate interactions, bioinformatics, protein engineering, and understanding the fundamental basis for enzyme catalysis. With the sequencing of the human genome and the genomes of hundreds of other species, Structural Genomics (SG) efforts are enabling the discovery of thousands of new protein structures. The next question is: What do these structures actually do? Prof. Ondrechen’s group is working on the development of methods to predict protein function from structure. Our THEMATICS method (see Ondrechen et al., Proc. Natl. Acad. Sci. USA 98, 12473, 2001) requires only the structure of the query protein and thus works for proteins that bear no resemblance to previously characterized proteins.

Current projects deal with: 1) Discovering the function of SG proteins expressed from the genome that are currently of unknown function; 2) Exploring the multilayer nature of enzyme active sites; 3) Using THEMATICS for the analysis of specific enzymes of biological and medical importance; and 4) Development and application of novel machine learning (ML) methodologies in order to utilize THEMATICS and other bioinformatics tools to identify protein interaction sites. We are working in partnership with the Institute for Complex Scientific Software (ICSS) at Northeastern University on the novel ML methodologies. We are also working in collaboration with experimentalists to test and verify our predictions pertaining to multilayer active sites and also to test our predicted functional annotations of Structural Genomics proteins.

(Picture shows residues predicted in and around the active site of PNGase F)

Selected Publications

“Prediction of Interaction Sites from Apo 3D Structures When the Holo Conformation is Different,” L.F. Murga, M.J. Ondrechen, and D. Ringe,
Proteins: Structure Function Bioinformatics 72:3, 980-992 (2008).

“Identification of a twin-arginine leader peptide binding site in DmsD; Defined through random and bioinformatics-directed mutagenesis,” C.S. Chan, T.M.L. Winstone, L. Chang, H. Li, C. Stevens, M.L. Workentine, Y. Wei, M.J. Ondrechen, M. Paetzel, and R.J. Turner, Biochemistry 47, 2749-2759 (2008).

“pH-dependent Interdomain Tethers of CD1b Regulate Its Antigen Capture,”
M. Relloso, T.-Y. Cheng, J.S. Im, E. Parisini, C. Roura-Mir, C. DeBono, D. M. Zajonc, L. F. Murga, M.J. Ondrechen, I.A. Wilson, S.A. Porcelli, and D.B. Moody,
Immunity 28, 774-786 (2008).