Understanding the relationship between protein structure and biological function has long been a major goal of structural biology. With the advent of many structural genomics projects, there is a practical need for tools to analyse and characterise the possible functional attributes for a new structure.
One of the major challenges in assigning function is to recognise a cognate ligand which may be a small molecule or a large macromolecule. At EBI we have been developing a range of methods which seek to annotate a functional site. These methods include:
Using sequence data and global and local structure comparisons to recognise distant relatives or short sequence patterns that are characteristic of binding sites. Using 3-dimensional templates for functional sites defined from proteins of known structure and function which can identify similarities between the query protein and other proteins in the PDB. Using spherical harmonics to define the shape of a binding site and to compare this shape with all known binding sites in the PDB and with the small molecule metabolome.
These methods have some success dependent upon the shape and flexibility of the binding site. In this presentation I will review our progress in this area and describe application to the sulpher transferases. Some of this work has been integrated into the ProFunc pipeline (coordinated by R.A. Laskowski) which is a web server which can provide automated annotation for a new protein structure. (http://www.ebi.ac.uk/thornton-srv/databases/ProFunc/).
Laskowski, R.A., Watson, J.D. & Thornton, J.M. (2005). ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res., 33, W89-W93. Laskowski, R.A., Watson, J.D. & Thornton, J.M. (2005) Protein function prediction using local 3D templates. J. Mol Biol., 351, 614-626. Morris, R.J., Kahraman, A. & Thornton, J.M. (2005) Binding pocket shape analysis for protein function prediction. Acta. Cryst. D61, C156-C157.