Tom Oldfield

The three-dimensional environments of ligand binding sites have been derived from the parsing and loading of the PDB entries into a relational database. For each bound molecule the biological assembly of the quaternary structure has been used to determine all contact residues and a fast interactive search and retrieval system has been developed. Prosite pattern and short sequence search options are available together with a novel graphical query generator for inter-residue contacts. The database and its query interface are accessible from the Internet through a web server located at: http://www.ebi.ac.uk/msd-srv/msdsite.

The polypeptide of a protein molecule can be considered as a chain of C alpha atoms linked by pseudobonds between the C alpha atoms of successive amino acid residues. This paper presents an analysis of the angle and dihedral angles made by these pseudobonds in protein structures determined at high resolution by X-ray crystallography. This analysis reveals a strong correlation between C alpha geometry and the protein fold. The regular features of protein secondary structure such as alpha-helix and beta-sheet are very clearly defined. In addition, it is possible to identify with some confidence the discrete populations of particular conformations of beta-turn. Comparison with the traditional Ramachandran type of plot demonstrates that an analysis of protein structure on the basis of C alpha geometry provides a richer description of protein conformation. In addition, the characteristics of this geometry could be a useful guide in model building of protein structure.

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).

With the advent of drug-design experiments where the interaction between a protein and a ligand is determined using X-ray crystallography, the use of automated methods for modelling the ligand into electron density represents a powerful tool. Once the protein structure has been determined by crystallography it is normal that subsequent ligand-complex structures are isomorphous, or nearly so, with the original structure and it is necessary only to determine the fit of ligand to any unsatisfied electron density. The X-LIGAND application was designed with this protocol in mind and provides a tool that searches for unsatisfied electron density and then fits flexible ligands to this within minutes without user intervention.