One of the paradigms that has evolved in modern biology states that the functional properties are conferred on proteins by virtue of their overall shape and conformation. In the post-genomics era, when sequences are becoming rapidly available, the gap between the availability of sequences and understanding their functions is ever-widening. It is in this context we are attempting to analyse structures of proteins so that they can be assigned biochemical functions based on their 3D conformation.

We demonstrated a few years ago an approach where hypothesis on the function of a protein could be proposed based on the knowledge of its structure derived by threading. In this case we hypothesized that an ORF annotated as hypothetical in the M. tuberculosis genome possessed the function as inositol-1-phosphate synthase. We further demonstrated by complementation in S. cerevisiae that indeed our hypothesis was correct. This was one of the first reports in literature where structural knowledge was being used for annotation of an ORF of unknown function.

In recent years we have focussed more on the relative juxtaposition of residues in proteins to propose their functions. In a recent report, we have been able to demonstrate that there are a number of PDB deposited structures, where the authors might have missed metal-binding sites. This may be due the absence of metal in the crystals of these proteins, or might even be false identification of a water molecule in that position. Based on this study, we have now made a web server, where putative active sites of proteins could be proposed with an input set of coordinates (http://sunserver.cdfd.org.in:8080/protease/). Currently we are attempting to enhance the scope of this approach (PAR-3D) to include as many known active sites in proteins as possible.