The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.[Supplemental material is available online at www.genome.org. Bioperl is available as open-source software free of charge and is licensed under the Perl Artistic License (http://www.perl.com/pub/a/language/misc/Artistic.html). It is available for download at http://www.bioperl.org. Support inquiries should be addressed to bioperl-l@bioperl.org.]

The disulfide bridge closed cyclic peptide corresponding to the whole Consensus V3 loop of the envelope protein gpl20 of HIV-1 was examined by proton 2D-NMR spectroscopy in water and in a 20% trifluoroethanol/water solution. In water, NOE data support a B-turn conformation for the central conservative GPGR region and point towards partial formation of a helix in the C-terminal part. Upon addition of trifluoroethanol, a C-terminal helix is formed. This is evidenced by NOE data, a-proton chemical shift changes and changes in the JNo vicinal coupling constants. The C-terminal helix is amphipathic and also occurs in other examined strains. It could therefore be an important feature for the functioning of the V3 loop.

The disulfide-bridge-closed cyclic peptide corresponding to the whole V3 loop of the R F HIV-1 strain was examined by proton two-dimensional NMR spectroscopy in water and water/trifluoroethanol solutions. Although most of the peptide is conformationally averaged in water, the NOE data support a pturn conformation for the central conservative GPGR region and the presence of nascent helix. Upon addition of trifluoroethanol, helix formation in the C-terminal part becomes apparent. This is confirmed by CD data. NOES indicative of multiple and transient p-turns around the Asn6 glycosylation site and NOES fitting X-ray data on a linear V3 peptide-Fab complex also emerge. The C-terminal helix is shown to have aniphipathic character and might thus assist in the infection process. Keywords: NMR; C D ; RF V3 loop; amphipathic helix; human immunodeficiency virus type I (HIV-I).The envelope glycoprotein gpl20 of human immunodeficiency virus type I (HIV-1) and its associated transmembrane glycoprotein gp41 play a direct role in the initial phase of infection of CD4-positive cells [I] and are the major targets of the humoral host immune response. After binding of gp120 to CD4 a conformational change in gp120 [2] disrupts the heterodimeric gp120-gp41 complex, exposing fusogenic domains at the N-terminal region of gp42 [3]. This ultimately results in virus-cellmembrane fusion [4]. A second domain corresponding to the third variable region (V3) of gp120 is also involved in this fusion step [5]. The V3 region is a surface-accessible loop formed by a disulfide bridge between two invariant cysteines at positions 303 and 338 of gp120 [6]. The exact mechanism by which HIV-1 enters host cells and the specific role of the V3 region in cell penetration have not yet been fully clarified. Antibodies directed towards the V3 loop do not affect gpl20-CD4 binding, but do prevent the subsequent cell infection [7]. Recent studies suggest that after gpl20-CD4 binding the highly conserved tip of the V3 loop is cleaved between Arg and Ala by a cell-surface protease and that this cleavage event is a requisite for viral infection [S, 91. Linear peptides corresponding to the central part of the V3 loop have been shown to inhibit membrane fusion and subsequent infection [lo].The V3 region is well exposed to the immune system and comprises the major antigenic determinant against which mostCorrespondence to E A. M. Borrernans, Biomolecular NMR Unit,

The disulfide bridge closed cyclic peptide corresponding to the whole V3 loop of the envelope protein gp120 of the ELI HIV-1 strain was synthesized and examined by proton 2D NMR spectroscopy in water. Although the peptide is mainly conformationally flexible, a turn appears to be present at an N-terminal glycosylation site, while in the C-terminal half of the peptide the data point toward nascent helical structures. Similar conformational preferences in aqueous solution were observed in other V3 loop peptides, especially for the Ile28-Gly30 tripeptide part.

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