SUMMARY: The PROSITE resource provides a rich and well annotated source of signatures in the form of generalized profiles that allow protein domain detection and functional annotation. One of the major limiting factors in the application of PROSITE in genome and metagenome annotation pipelines is the time required to search protein sequence databases for putative matches. We describe an improved and optimized implementation of the PROSITE search tool pfsearch that, combined with a newly developed heuristic, addresses this limitation. On a modern x86_64 hyper-threaded quad-core desktop computer, the new pfsearchV3 is two orders of magnitude faster than the original algorithm. AVAILABILITY AND IMPLEMENTATION: Source code and binaries of pfsearchV3 are freely available for download at http://web.expasy.org/pftools/#pfsearchV3, implemented in C and supported on Linux. PROSITE generalized profiles including the heuristic cut-off scores are available at the same address.

Modern biology has become a science of information, analysis and prediction, coalescing into computational biology -- a single discipline at the crossroads of life sciences, informatics, and mathematics. New developments in information and communications technology as well as high-performance computing enable researchers to address new demanding scientific problems which seemed far out of reach only a few years ago. The computational requirements of most applications in computational biology differ significantly from the requirements of other users of highthroughput computing such as high energy physics. To address these needs, the SwissBioGrid initiative, a collaboration among several partner institutions with a broad spectrum of expertise, was started over a year ago. In this paper, we report on its current status and achievements as well as the lessons learned which are of interest to the wider e-Science and Grid communities.

Bioinformatics algorithms such as sequence alignment methods based on profile-HMM (Hidden Markov Model) are popular but CPU-intensive. If large amounts of data are processed, a single computer often runs for many hours or even days. High performance infrastructures such as clusters or computational Grids provide the techniques to speed up the process by distributing the workload to remote nodes, running parts of the work load in parallel. Biologists often do not have access to such hardware systems. Therefore, we propose a new system using a modern Grid approach to optimise an embarrassingly parallel problem. We achieve speed ups by at least two orders of magnitude given that we can use a powerful, world-wide distributed Grid infrastructure. For large-scale problems our method can outperform algorithms designed for mid-size clusters even considering additional latencies imposed by Grid infrastructures.

Among the various databases dedicated to the identification of protein families and domains, PROSITE is the first one created and has continuously evolved since. PROSITE currently consists of a large collection of biologically meaningful motifs that are described as patterns or profiles, and linked to documentation briefly describing the protein family or domain they are designed to detect. The close relationship of PROSITE with the SWISS-PROT protein database allows the evaluation of the sensitivity and specificity of the PROSITE motifs and their periodic reviewing. In return, PROSITE is used to help annotate SWISS-PROT entries. The main characteristics and the techniques of family and domain identification used by PROSITE are reviewed in this paper.

MOTIVATION: InterPro is a new integrated documentation resource for protein families, domains and functional sites, developed initially as a means of rationalising the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. RESULTS: Merged annotations from PRINTS, PROSITE and Pfam form the InterPro core. Each combined InterPro entry includes functional descriptions and literature references, and links are made back to the relevant parent database(s), allowing users to see at a glance whether a particular family or domain has associated patterns, profiles, fingerprints, etc. Merged and individual entries (i.e. those that have no counterpart in the companion resources) are assigned unique accession numbers. Release 1.2 of InterPro (June 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification (PTMs) encoded by 6581 different regular expressions, profiles, fingerprints and Hidden Markov Models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1000000 hits from 264333 different proteins out of 384572 in SWISS-PROT and TrEMBL).