Prof. Ondrechen’s research group specializes in theoretical and computational chemistry and computational biology. Areas of interest include: 1) Understanding the fundamental basis for enzyme catalysis; 2) Functional genomics – prediction of the functional roles of gene products (proteins); 3) Modeling of enzyme-substrate interactions; 4) Drug discovery; 5) Bioinformatics; and 6) Protein engineering.
With the sequencing of the human genome and the genomes of hundreds of species of interest, Structural Genomics (SG) projects have now reported over 13,000 new protein structures. The next question is: What do these structures actually do? Prof. Ondrechen’s group is developing methods to predict protein function from structure. Our THEMATICS (see Ondrechen et al., Proc. Natl. Acad. Sci. USA 98, 12473, 2001) and POOL (see Tong, Wei, Murga, Ondrechen and Williams, PLoS Computational Biology, 2009) methods predict the residues involved in biochemical function, require only the structure of the query protein, and thus work for proteins that bear no resemblance to previously characterized proteins. Our SALSA method (see Wang, Yin, et al. 2013) uses these predicted functional residues to determine biochemical function.
Another current project explores the multilayer nature of enzyme active sites – we are able to predict when remote amino acid residues are involved in catalysis. We work in collaboration with experimentalists to test and verify our predictions pertaining to multilayer active sites. This is a very important question for enzyme design.
With the many very active programs in Medicinal Chemistry in this Department, the Ondrechen group also provides computational collaboration for multiple different drug discovery efforts.