MOTIVATION: Protein sequence comparison has become a major tool for biologists. Various methods have been designed in order to reveal even remote homologies among proteins. Sequence analyses are powerful, but the lower the identity score, the more skill and time are required to perform them accurately. While necessary to confirm the sequence comparison through the potential of mean force, sequence alignment and molecular modelling are still tedious and time-consuming tasks. RESULTS: In order to help sequence threading onto known three-dimensional (3D) structures, we have developed a new program, named TITO (Tool for Incremental Threading Optimization), which uses a multiple alignment to validate and help the refinement of a sequence/structure comparison. It measures the compatibility of a family of related sequences with a known 3D structure. The coordinates of the common core are extracted, allowing further molecular modelling and 3D survey. AVAILABILITY: TITO is available by anonymous ftp at: ftp://lmcp.jussieu. fr/pub/tito CONTACT: [email protected] SUPPLEMENTARY INFORMATION: http://www.lmcp.jussieu.fr/ approximately labesse/TITO/TITO.html

MOTIVATION: When routinely analysing protein sequences, detailed analysis of database search results made with BLAST and FASTA becomes exceedingly time consuming and tedious work, as the resultant file may contain a list of hundreds of potential homologies. The interpretation of these results is usually carried out with a text editor which is not a convenient tool for this analysis. In addition, the format of data within BLAST and FASTA output files makes them difficult to read. RESULTS: To facilitate and accelerate this analysis, we present for the first time, two easy-to-use programs designed for interactive analysis of full BLAST and FASTA output files containing protein sequence alignments. The programs, Visual BLAST and Visual FASTA, run under Microsoft Windows 95 or NT systems. They are based on the same intuitive graphical user interface (GUI) with extensive viewing, searching, editing, printing and multithreading capabilities. These programs improve the browsing of BLAST/FASTA results by offering a more convenient presentation of these results. They also implement on a computer several analytical tools which automate a manual methodology used for detailed analysis of BLAST and FASTA outputs. These tools include a pairwise sequence alignment viewer, a Hydrophobic Cluster Analysis plot alignment viewer and a tool displaying a graphical map of all database sequences aligned with the query sequence. In addition. Visual Blast includes tools for multiple sequence alignment analysis (with an amino acid patterns search engine), and Visual FASTA provides a GUI to the FASTA program.

MOTIVATION: The secondary structure is a key element of architectural organization in proteins. Accurate assignment of the secondary structure elements (SSE) (helix, strand, coil) is an essential step for the analysis and modelling of protein structure. Various methods have been proposed to assign secondary structure. Comparative studies of their results have shown some of their drawbacks, pointing out the difficulties in the task of SSE assignment. RESULTS: We have designed a new automatic method, named P-SEA, to assign efficiently secondary structure from the sole C alpha position. Some advantages of the new algorithm are discussed. AVAILABILITY: The program P-SEA is available by anonymous ftp: ftp.lmcp.jussieu.fr directory: pub/.

Hydrophobic cluster analysis (HCA) is an efficient method for analysing and comparing the amino acid sequences of proteins. It relies on two-dimensional representations of the sequences presently generated by simple plot programs working on microcomputers. Two interactive programs, MANSEK and SUNHCA, are described here that operate from Vax and Sun workstations respectively. These programs allow the display of several protein sequences in the form of two-dimensional helical plots suitable for HCA. Several tedious, repetitive and time-consuming steps of HCA have been suppressed by implementing several features such as interactive on-screen manipulations (zoom, translations) of the plots and HCA score calculations on segments chosen by the user. Plots on paper can be obtained through hard copies or plotting subroutines.

OMEGA is a compilation of recent structural information on proteins derived from X-ray crystallography or NMR and published in journals referenced by Current Contents. To date, 401 entries have been included (334 X-ray, 28 NMR, 5 NMR + X-ray, 5 electron microscopy, 3 neutron scattering, 2 neutron diffraction, 1 electron microscopy + X-ray, 12 model, 11 miscellaneous), with 5-10 new proteins being added each week. OMEGA can be accessed on Macintosh and is interrogated through 32 key words (space group, resolution, secondary structure, number of residues, etc). This pool of proteins could be used for various purposes, including searches for proteins with a particular set of secondary structures. OMEGA will be continuously updated (every 6 months) and may later include all proteins already reported in the PDB, as well as structures reported in journals with smaller readerships.

A BASIC program, HCABAND, is described which is used to convert the linear amino acid sequence of proteins into a word processor-readable file to generate the 2D-helical representation required for hydrophobic cluster analysis. The user can specify the width of the plot and can use the word processor macro-commands to facilitate visual inspection of the plots. The plots can be easily stored on diskettes, mixed with text and printed. HCABAND features are generally applicable and can be implemented on virtually any microcomputer.