RPBS: a web resource for structural bioinformatics.

RPBS (Ressource Parisienne en Bioinformatique Structurale) is a resource dedicated primarily to structural bioinformatics. It is the result of a joint effort by several teams to set up an interface that offers original and powerful methods in the field. As an illustration, we focus here on three such methods uniquely available at RPBS: AUTOMAT for sequence databank scanning, YAKUSA for structure databank scanning and WLOOP for homology loop modelling.

Filtering redundancies for sequence similarity search programs.

Database scanning programs such as BLAST and FASTA are used nowadays by most biologists for the post-genomic processing of DNA or protein sequence information (in particular to retrieve the structure/function of uncharacterized proteins). Unfortunately, their results can be polluted by identical alignments (called redundancies) coming from the same protein or DNA sequences present in different entries of the database. This makes the efficient use of the listed alignments difficult.

Automat and BLAST: comparison of two protein sequence similarity search programs.

Since the early 1980s, protein/DNA sequence similarity search has become of major importance to biologists, and the need for fast and efficient tools grows with the size of databanks. Two programs use the strategy of finite state deterministic automatons to accomplish these searches. One of these two is BLAST, which is now widely used, and the other Automat, which has just been published.

Automat: a novel software system for the systematic search for protein (or DNA) similarities with a notable application to autoimmune diseases and AIDS.

Automat is a novel program which finds exhaustively all the oligopeptide segments shared by a given protein of any size with the proteins of a whole databank. It allows the user to collect statistics on the composition of the sequence studied in reference to the databank used. We present here the rationale and the algorithm underlying this powerful software.

HIV-1-induced immune suppression may result from autoimmune disorders including anti-SLWDQ autoantibodies.

We have previously unravelled the striking SLWDQ pentapeptide identity between HIV-1 env gp120 and the CD4 molecule. We show here that this pentapeptide is required for the functioning of the co-stimulatory MHC-CD4 signal in T4-cell activation since it suppresses antigen-induced T-cell proliferation. Moreover, concerning the MHC class II counterpart, the LNGQEETGVVSTN sequence which strongly inhibits T-cell immune activation is likely to be part of the functional site of the molecule.

Striking similarities between HIV-1 Env protein and the apoptosis mediating cell surface antigen Fas. Role in the pathogenesis of AIDS.

We have designed a computer strategy in order to detect systematically peptidic sites with the potential of interfering with the immune regulatory processes. Applying this software to HIV-1 proteins has led us to unravel a few peptidic sites which could either act directly or be the targets of an auto-immune reaction during HIV-1 infection. We previously reported that the SLWDQ pentapeptide identity with a critical site of CD4 could trigger in HIV-1 infected individuals both an humoral and a cellular autoimmune reaction.

Critical sites: a semantic approach to protein sequences. Application to the HIV-1 envelope molecule.

We have designed two software systems allowing the study of proteins through a comparison to those stored in data banks. The first one, "Automat", locates in a systematic manner all identities shared by a given protein and the proteins in a data bank. The second, "Critic" enables the selection of specific segments in a given molecule by comparing them with those gathered in a data bank.