APPLICATIONS PRODUCTS BASED ON CRYSTALLOGRAPHIC DATA
I. Bruno, K.J. Lipscomb; CCDC, CB2 1EZ Cambridge, UK
Over the past few years, CCDC has added to its work on collating and distributing the Cambridge Structural Database (CSD) System by making use of the knowledge contained therein in applications programs, designed to approach problems in the life sciences. There are two main programs in this area - GOLD and SuperStar - but also there is Relibase+.
Relibase+ is a protein-ligand search and analysis system, designed primarily for use on the protein-ligand complexes stored within the Protein Data Bank (indeed, a free version of the program, Relibase, is available for anyone to use on the web at http://relibase.ccdc.cam.ac.uk and two mirror sites). It also contains extra facilities to enable users to produce their own, in-house databases of proprietary structures, which can then be searched alongside the publically available PDB entries. Relibase+ is constantly being developed, with recent improvements including a new crystal packing module, enabling investigation of crystallographic packing effects around ligand binding sites, and ReliScript, a Python-based toolkit which allows users access to enhanced PDB data and search methods.
The well-established GOLD program for protein-ligand docking has been heavily enhanced to facilitate its use in virtual screening studies. Genetic algorithm settings have been optimised, the program has been adapted for use in parallel on clusters of machines, and forthcoming are versions of the program for distributed GRID computing, and improvements to post-processing to account for large volumes of data.
SuperStar relies upon the IsoStar knowledge-based library of intermolecular interactions for its function, which is to identify binding "hotspots" for particular organic functional groups within a binding site. SuperStar maps can now be produced from either the CSD-derived or PDB-derived scatterplots in IsoStar and the speed of the calculations has been increased by application of parameterised scatterplot representations.