Research Interests
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The primary goal of the lab is to understanding biology at the molecular level using computational methods. I am also interested in developing methodologies for improving experimental techniques used in molecular biology studies. Wet-lab research is done in collaboration with other Faculty in the Institute and elsewhere. Students from any background with interest in biology and no inhibition in Math and Computer Programming may contact me for prospective research positions. The broad area of research interests are mentioned below. (Please note that I do not take summer interns except for under fellowship from the Indian Science Academies. Also if you want to do your M.Sc./M.Phil/B.Tech. project in my laboratory, the minimum time should be 6 months. Any application below the mentioned time will not be entertained.)
1.	Genome-wide function annotation.
Sequence similarity and signature sequence based search methods are most used for annotating function. They work reasonably well when there is a match (within some stated threshold) with a functionally elucidated protein in the query database. They fail most of the time when there are no significant matches. Currently, a large number of ORFs from genome sequencing projects show little or no significant match with functionally known proteins. They represent a large pool of genes that need to be understood for any meaningful progress of biology. In my previous work I have developed a metaserver based method to assign function to such novel proteins. This method, although very powerful, can be improved further in coverage and accuracy. The results from the predictions are of fundamental value to all biologists.
2.	Understanding interaction networks in biology
Each molecule in the cell has certain functions. But these functions are not perfomed alone. For example: an enzyme working on a substrate produces a new product. This new product is not the end of the reaction cycle. It may be a substrate for another enzyme. If the reaction is propagated, it forms, what is known as a reaction pathway. But pathways are not formed only by enzymes, but by almost all molecules in the cell, because they require to work in concert to maintain the cellular viability. For example, a series of transporters may form pathways to funnel ion from the extrcellular region to the cytosol. If you open a biology book, you can see examples of many such pathways: apoptosis pathway, the secretory pathway and so on. All such pathways are interlinked together in the cell forming a very sophisticated interaction network that form the basis of cellular homeostasis. Understanding the networks and their interaction is one of the most challenging problems in modern biology. Many large-scale genomic, proteomics, transcriptomic, metabolomic experiments give us a large body of data (publicly available) which could be used to build potential models of interaction networks. They are very useful in understanding cellular pathways, and are a stepping stone to meaningful drug design and targeting.
3.	Principles of protein structure and conformation.
The work of Pauling and coworkers laid a rational foundation for the presence a-helix and b-sheet in protein structures. Our own G.N. Ramachandran and coworkers showed how using a simple sterical basis one can disallow certain backbone conformation in proteins. A lot more work has been done over the last four decades to understand protein fold and conformation. However, the protein folding problem is still elusive and a lot more remains to be understood on how proteins fold and form certain conformations in specific environments. Of particular interest to me are the understanding of the effects of the weaker interactions in stabilizing protein structures.
4.	Ligand and ion binding sites in proteins.
The surface of the protein molecule is adapted to bind diverse ligands, ions and other proteinaceous and nonproteinaceous molecules in the cell. We still poorly understand as to which surface is adapted to bind what kind of ion or ligand. Shape complementarity, charge complementarity and other physico-chemical compatibility parameters have been used to understand docking of ligands and ions. While there are methods available to analyze protein surfaces and the kind of ligands they bind, they are effective only with large binding sites with significant physico-chemical attributes. There exists no general method that can predict docking of all kinds of ligands and ions with reasonable accuracy.
5.	Drug targeting and development.
The studies mentioned above have a potential to unravel numerous targets for drugs development. I am interested in identifying natural compounds that have properties facile to bind the targeted receptors. Understanding therapeutics in alternative medicine systems is one of my interest.
6.	Development of protein-complex recognition method.
Currently, protein-protein docking methods are being evaluated through the CAPRI competitions. Results from this docking competition show that we are not able to decipher interacting surface(s) for the protein complex very easily. We require better scoring functions that can distinguish between interacting and non interacting parts. We look to develop a protein-complex recognition method with the view to improve prediction of protein-protein interaction surfaces.
7.	Data mining protein crystallization databases.
Crystallization of biological macromolecules remain an art rather than a science. We need to develop proper protein crystallogenesis theory to be able to advance structural biology efforts. Large databases are publicly available which can be mined to understand crystallogenesis better. The inferences can be applied to difficult proteins belonging to the Faculty in the Institute and elsewhere as proof of principle.
8.	Development of Laboratory Information Systems.
As technology gets advanced, systems get automated. Integrating these systems so that the data generated be properly archived and harvested is of paramount importance. I am interested in developing software that can be used by laboratory personnel or integrated with laboratory equipments so that the data can archived and subsequently mined for future analysis.