The Classification of Protein Domains.

The significant expansion in protein sequence and structure data that we are now witnessing brings with it a pressing need to bring order to the protein world. Such order enables us to gain insights into the evolution of proteins, their function and the extent to which the functional repertoire can vary across the three kingdoms of life. This has lead to the creation of a wide range of protein family classifications that aim to group proteins based upon their evolutionary relationships.

The classification of protein domains.

The significant expansion in protein sequence and structure data that we are now witnessing brings with it a pressing need to bring order to the protein world. Such order enables us to gain insights into the evolution of proteins, their function, and the extent to which the functional repertoire can vary across the three kingdoms of life. This has led to the creation of a wide range of protein family classifications that aim to group proteins based on their evolutionary relationships.

Target selection for structural genomics: an overview.

The success of the whole genome sequencing projects brought considerable credence to the belief that high-throughput approaches, rather than traditional hypothesis-driven research, would be essential to structurally and functionally annotate the rapid growth in available sequence data within a reasonable time frame. Such observations supported the emerging field of structural genomics, which is now faced with the task of providing a library of protein structures that represent the biological diversity of the protein universe. To run efficiently, structural genomics projects aim to define a set of targets that maximize the potential of each structure discovery whether it represents a novel structure, novel function, or missing evolutionary link.

Towards a comprehensive structural coverage of completed genomes: a structural genomics viewpoint.

Background: Structural genomics initiatives were established with the aim of solving protein structures on a large-scale. For many initiatives, such as the Protein Structure Initiative (PSI), the primary aim of target selection is focussed towards structurally characterising protein families which, so far, lack a structural representative. It is therefore of considerable interest to gain insights into the number and distribution of these families, and what efforts may be required to achieve a comprehensive structural coverage across all protein families.

Exploiting protein structure data to explore the evolution of protein function and biological complexity.

New directions in biology are being driven by the complete sequencing of genomes, which has given us the protein repertoires of diverse organisms from all kingdoms of life. In tandem with this accumulation of sequence data, worldwide structural genomics initiatives, advanced by the development of improved technologies in X-ray crystallography and NMR, are expanding our knowledge of structural families and increasing our fold libraries. Methods for detecting remote sequence similarities have also been made more sensitive and this means that we can map domains from these structural families onto genome sequences to understand how these families are distributed throughout the genomes and reveal how they might influence the functional repertoires and biological complexities of the organisms.

Comprehensive genome analysis of 203 genomes provides structural genomics with new insights into protein family space.

We present an analysis of 203 completed genomes in the Gene3D resource (including 17 eukaryotes), which demonstrates that the number of protein families is continually expanding over time and that singleton-sequences appear to be an intrinsic part of the genomes. A significant proportion of the proteomes can be assigned to fewer than 6000 well-characterized domain families with the remaining domain-like regions belonging to a much larger number of small uncharacterized families that are largely species specific. Our comprehensive domain annotation of 203 genomes enables us to provide more accurate estimates of the number of multi-domain proteins found in the three kingdoms of life than previous calculations.

Gene3D: modelling protein structure, function and evolution.

The Gene3D release 4 database and web portal (http://cathwww.biochem.ucl.

Protein structure prediction servers at University College London.

A number of state-of-the-art protein structure prediction servers have been developed by researchers working in the Bioinformatics Unit at University College London. The popular PSIPRED server allows users to perform secondary structure prediction, transmembrane topology prediction and protein fold recognition. More recent servers include DISOPRED for the prediction of protein dynamic disorder and DomPred for domain boundary prediction.

Progress of structural genomics initiatives: an analysis of solved target structures.

The explosion in gene sequence data and technological breakthroughs in protein structure determination inspired the launch of structural genomics (SG) initiatives. An often stated goal of structural genomics is the high-throughput structural characterisation of all protein sequence families, with the long-term hope of significantly impacting on the life sciences, biotechnology and drug discovery. Here, we present a comprehensive analysis of solved SG targets to assess progress of these initiatives.

Identification and distribution of protein families in 120 completed genomes using Gene3D.

Using a new protocol, PFscape, we undertake a systematic identification of protein families and domain architectures in 120 complete genomes. PFscape clusters sequences into protein families using a Markov clustering algorithm (Enright et al., Nucleic Acids Res 2002;30:1575-1584) followed by complete linkage clustering according to sequence identity.

The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis.

The CATH database of protein domain structures (http://www.biochem.ucl.

A practical and robust sequence search strategy for structural genomics target selection.

Motivation: Target selection strategies for structural genomic projects must be able to prioritize gene regions on the basis of significant sequence similarity with proteins that have already been structurally determined. With the rapid development of protein comparison software a robust prioritization scheme should be independent of the choice of algorithm and be able to incorporate different sequence similarity thresholds.

Results: A robust target selection strategy has been developed that can assign a priority level to all genes in any genome.

Rapid protein domain assignment from amino acid sequence using predicted secondary structure.

The elucidation of the domain content of a given protein sequence in the absence of determined structure or significant sequence homology to known domains is an important problem in structural biology. Here we address how successfully the delineation of continuous domains can be accomplished in the absence of sequence homology using simple baseline methods, an existing prediction algorithm (Domain Guess by Size), and a newly developed method (DomSSEA). The study was undertaken with a view to measuring the usefulness of these prediction methods in terms of their application to fully automatic domain assignment.