Human Diseases and SNPS.

The single nucleotide polymorphisms are cause of many human diseases. Our group is developing models to predict deleterious mutations on basis of protein stability by modeling impact of mutations on protein structure. The models have been applied to all known missense mutation in the human (www.snps3d.org). We are also developing tools to help us understand complex traits by in the context of protein-protein interactions.

Structural Genomics.

The Structural Genomics aims to determine 3D structure of proteins for all protein families. There are currently two ongoing structural genomics projects we are working on. The first one, Structure 2 Function project, has been funded for 5 years and it is now entering its final phase. The second project, Alternative Splicing Structural Genomics project, is in its first year of funding and we are in preparatory phase of the project. Our group is heavily involved in analyzing the alternative splicing transcript, prioritizing and selecting targets for crystallization and NMR studies.

Alternative Splicing

Alternative splicing is a common phenomenon in higher eukaryotes. A single pre-mRNA can produce many different mRNA and protein products. It is believed that many of these protein products are responsible for diversify and fine tuning the functions of biological system. We are working on methods to predict functionality of transcripts on basis of their impact on protein structure.

Horizontal Transfer and Operons in Bacteria

The horizontal transfer is believed to play major role in evolution of bacterial species. Accurate reconstruction of bacterial evolution requires development of methods that take horizontal transfer into account. Our group is working on algorithms for accurate reconstruct protein families, molecular clocks and evolutionary trees.

Prediction of protein structure.

One of the most challenging problems in biology is prediction of protein 3D structure. Although our focus has shifted toward evolutionary aspects of biology, we are still actively involved in structure prediction field. Our efforts has focus in number of areas of protein structure prediction, ab-initio folding via genetic algorithms, development of full atom potentials, graph theory approaches to building loops and exploring side-chain packing, sequence profile-profile alignments, homology model refinement, and many others.