Funding for cancer research by an Indian funding agency, DBT.

Cancer is a group of diseases with major societal impact and accounts for approximately 55 percent of mortality in India. The Indian population is increasing in size and gradually ageing. As a result, the number of people diagnosed with and dying of cancer are increasing. Government funding agencies such as the Department of Biotechnology (DBT) has a clear definitive role in the management and control of cancer. Through Research and Development programs and multi-institutional networking programs, DBT has provided resources to individual investigators and to institutions, to carry out basic, applied, translational and clinical research and to develop new methods to prevent and treat disease and to conduct research especially in challenging areas pertaining to different types of cancer. This article summarizes the funding provided by DBT for different cancer research programs.

Proteins: sequence to structure and function--current status.

In an era that has been dominated by Structural Biology for the last 30-40 years, a dramatic change of focus towards sequence analysis has spurred the advent of the genome projects and the resultant diverging sequence/structure deficit. The central challenge of Computational Structural Biology is therefore to rationalize the mass of sequence information into biochemical and biophysical knowledge and to decipher the structural, functional and evolutionary clues encoded in the language of biological sequences. In investigating the meaning of sequences, two distinct analytical themes have emerged: in the first approach, pattern recognition techniques are used to detect similarity between sequences and hence to infer related structures and functions; in the second ab initio prediction methods are used to deduce 3D structure, and ultimately to infer function, directly from the linear sequence. In this article, we attempt to provide a critical assessment of what one may and may not expect from the biological sequences and to identify major issues yet to be resolved. The presentation is organized under several subtitles like protein sequences, pattern recognition techniques, protein tertiary structure prediction, membrane protein bioinformatics, human proteome, protein-protein interactions, metabolic networks, potential drug targets based on simple sequence properties, disordered proteins, the sequence-structure relationship and chemical logic of protein sequences.

ProRegIn: a regularity index for the selection of native-like tertiary structures of proteins.

Automated protein tertiary structure prediction from sequence information alone remains an elusive goal to computational prescriptions. Dividing the problem into three stages viz. secondary structure prediction, generation of plausible main chain loop dihedrals and side chain dihedral optimization, considerable progress has been achieved in our laboratory (http://www.scfbio-iitd.res.in/bhageerath/index.jsp) and elsewhere for proteins with less than 100 amino acids. As a part of our on-going efforts in this direction and to facilitate tertiary structure selection/rejection in containing the combinatorial explosion of trial structures for a specified amino acid sequence, we describe here a web-enabled tool ProRegIn (Protein Regularity Index) developed based on the regularity in the Phi, Psi dihedral angles of the amino acids that constitute loop regions. We have analysed the dihedrals in loop regions in a non-redundant dataset of 7351 proteins drawn from the Protein Data Bank and categorized them as helix-like or sheet-like (regular) or irregular. We noticed that the regularity thus defined exceeds 86% for Phi barring glycine and 70% for Psi for all the amino acid side chains including glycine, compelling us to reexamine the conventional view that loops are irregular regions structurally. The regularity index is presented here as a simple tool that finds its application in protein structure analysis as a discriminatory scoring function for rapid screening before the more compute intensive atomic level energy calculations could be undertaken. The tool is made freely accessible over the internet at www.scfbio-iitd.res.in/software/proregin.jsp.

Bhageerath: an energy based web enabled computer software suite for limiting the search space of tertiary structures of small globular proteins.

We describe here an energy based computer software suite for narrowing down the search space of tertiary structures of small globular proteins. The protocol comprises eight different computational modules that form an automated pipeline. It combines physics based potentials with biophysical filters to arrive at 10 plausible candidate structures starting from sequence and secondary structure information. The methodology has been validated here on 50 small globular proteins consisting of 2-3 helices and strands with known tertiary structures. For each of these proteins, a structure within 3-6 A RMSD (root mean square deviation) of the native has been obtained in the 10 lowest energy structures. The protocol has been web enabled and is accessible at http://www.scfbio-iitd.res.in/bhageerath.

Major antifungal activity from the bulbs of Indian squill Urginea indica is a chitinase.

We have identified a chitinase with antifungal activity in the bulbs of the plant Urginea indica(Indian squill) and purified it about 26-fold. The purified preparation contained a Mr 29 kDa protein that was an active growth inhibitor of the fungal pathogens Fusarium oxysporum and Rhizoctonia solani in an in vitro assay. Amino acid sequence analysis of the Mr 29 kDa protein revealed it to be highly homologous to the family 19 glycoside hydrolases, which are known to possess chitinase activity. The U. indica chitinase lacked a cysteine-rich N-terminal domain (characteristic of class I chitinases) and contained a conserved motif indicative of the signature 1 of family 19 glycoside hydrolases. It shared a approximately 70% sequence identity with the 26 kDa endochitinase of Hordeum vulgare, a typical class II chitinase of family 19. The five cysteines in the partial sequence of the Mr 29 kDa chitinase were found to be identical in location to five of the seven cysteines present in the catalytic domain of the H. vulgare enzyme. The molecular weight, the lack of an N-terminal cysteine-rich sequence, and the striking identity to the H. vulgare endochitinase suggest that the Mr 29 kDa U. indica protein is a putative class II chitinase. The antifungal activity is presumably mediated through the chitinolytic activity of the Mr 29 kDa protein.