Bioinformatics Advance Access originally published online on January 24, 2006
Bioinformatics 2006 22(7):887-888; doi:10.1093/bioinformatics/btl019
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VISSA: a program to visualize structural features from structure sequence alignment
Burnham Institute for Medical Research La Jolla, CA 92037, USA
*To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT 1 INTRODUCTION2 IMPLEMENTATION3 RESULTSREFERENCES |
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Motivation: Multiple sequence alignment is an important tool to understand and analyze functions of homologous proteins. However, the logic of residue conservation/variation is usually apparent only in three-dimensional (3D) space, not on a primary sequence level. Thus, in a traditional multiple alignment it is often difficult to directly visualize and analyze key residues because they are masked by other residues along the alignment. Here we present an integrated multiple alignment and 3D structure visualization program that can (1) map and highlight residues from a 1D alignment onto a 3D structure and vice versa and (2) display only the alignment of preselected, key residues. This program, called Visualize Structure Sequence Alignment, also has many other built-in tools that can help analyze multiple sequence alignments.
Availability: http://bioinformatics.burnham.org/liwz/vissa
Contact: liwz{at}burnham.org
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1 INTRODUCTION |
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TOPABSTRACT1 INTRODUCTION2 IMPLEMENTATION3 RESULTSREFERENCES |
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Multiple sequence alignment is an important tool to study the evolution and function of homologous proteins. Popular algorithms for creating multiple sequence alignment include ClustalW (Thompson et al., 1994), Dalign (Morgenstern, 1999), T-Coffee (Notredame et al., 2000), POA (Lee et al., 2002), muscle (Edgar, 2004) and many others. In addition, many programs to edit and visualize the alignments, such as ClustalX (Thompson et al., 1997), Mview (Brown et al., 1998), Jalview (Clamp et al., 2004) and BoxShade, are also available. They use various coloring schemes to visualize variations of amino acids and identify conserved residues.
A common problem in visualizing and displaying a multiple sequence alignment is that in many cases key residues may be close in three-dimensional (3D) space but not on a primary sequence level, so it is difficult to focus on them while they are embedded in a long sequence alignment. Another related problem, given a protein and its 3D structure, is finding the conservation or mutation pattern of certain residues of interest at a specific 3D position, which requires seamless integration between the multiple sequence alignment and the 3D structures.
Many programs for visualizing protein 3D structures cannot provide multiple sequence alignments. And the multiple sequence alignment programs mentioned above usually cannot display 3D structures. In fact, matching multiple sequence alignments and 3D structures is often not straightforward because (1) the sequence of the same protein from an alignment and a PDB file are often different due to missing or mutated residues or artificial tags, and (2) residue numbers are also often different. When sequences are long or 3D structures are large, matching residues back and forth is a very tedious and boring task.
Several recent programs, including Pfaat (Johnson et al., 2003), ViTO (Catherinot and Labesse, 2004) and Friend (Abyzov et al., 2005), introduced functions to simultaneously visualize multiple alignments and 3D structures. Pfaat was designed for protein family analysis purpose; ViTO's goal was to help refinement of sequence-structure alignment for homology modeling; and Friend was an integrated interface for visualization of multiple structures and sequences.
Here we present a new program that can visualize both multiple sequence alignments and 3D structures. Our goal was to help researchers handle many practical issues involving simultaneous analysis of both sequence alignments and 3D structures, for example, checking what the conservation of residues around the active site is. Compared to other programs, we put more efforts so that users can easily map, highlight, and analyze any subset of residues of interest in 3D structures and an alignment. It also provided functions to present analysis results of such subset with publication-quality image, for example, it can show a condensed alignment of only a subset. The program can also handle various discrepancies of sequences between PDB files and alignments.
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2 IMPLEMENTATION |
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TOPABSTRACT1 INTRODUCTION2 IMPLEMENTATION3 RESULTSREFERENCES |
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VIsualize Structure Sequence Alignment (VISSA) has the following components: a multiple sequence alignment generator, an alignment viewer, a 3D structure viewer, and supporting tools. In VISSA, we use ClustalW and Rasmol as the alignment generator and structure viewer, respectively, due to their wide user base and great availability. The alignment viewer and all other supporting tools are implemented from scratch.
Many supporting tools are also integrated into the VISSA program. For instance, residues between PDB structures and alignments are matched by a pairwise alignment between the sequence read from the PDB file and the sequence used in the alignment. So, it can handle many common sequence variation cases in PDB such as insertions, deletions, tags, mutations, and residue modifications.
VISSA was developed and tested on a RedHat Linux system, and was written in Perl. The alignment viewer has a graphic user interface to display alignments and to perform various user commands; it was implemented with Perl/Tk.
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3 RESULTS |
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TOPABSTRACT1 INTRODUCTION2 IMPLEMENTATION3 RESULTSREFERENCES |
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The Figure 1 shows screen shots of several windows of VISSA program. It has one alignment window and can have any number of Rasmol windows. A user can select any set of residues from the alignment window and let the program highlight them in the Rasmol window, or the user can perform reverse mapping.
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The graphic user interface allows users to change font size, modify the coloring scheme of amino acids, switch the display of residue numbers, switch the display of certain sequences or residues, select proteins or residues, delete proteins, run or rerun alignments, edit an alignment, save results, export an alignment, define a structural site, define protein rendering options in Rasmol, change program parameters such as consensus threshold, and so on. The program has a tool that can cluster proteins into groups. A unique feature is that it can perform clustering based only on selected residues rather than on a full-length sequence.
This program will be under regular maintenance. We are also open to adding new functions in the future depending on users' suggestions.
Conflict of Interest: none declared.
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FOOTNOTES |
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Associate Editor: Dmitrij Frishman
Received on December 9, 2005; revised on January 18, 2006; accepted on January 23, 2006
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REFERENCES |
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TOPABSTRACT1 INTRODUCTION2 IMPLEMENTATION3 RESULTSREFERENCES |
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Abyzov, A., et al. (2005) Friend, an integrated analytical front-end application for bioinformatics. Bioinformatics, 21, 3677–3678
Brown, N.P., et al. (1998) MView: a web-compatible database search or multiple alignment viewer. Bioinformatics, 14, 380–381
Catherinot, V. and Labesse, G. (2004) ViTO: tool for refinement of protein sequence-structure alignments. Bioinformatics, 20, 3694–3696
Clamp, M., et al. (2004) The Jalview Java alignment editor. Bioinformatics, 20, 426–427
Edgar, R.C. (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res, . 32, 1792–1797
Johnson, J.M., et al. (2003) Protein family annotation in a multiple alignment viewer. Bioinformatics, 19, 544–545
Lee, C., et al. (2002) Multiple sequence alignment using partial order graphs. Bioinformatics, 18, 452–464
Morgenstern, B. (1999) DIALIGN 2: improvement of the segment-to-segment approach to multiple sequence alignment. Bioinformatics, 15, 211–218
Notredame, C., et al. (2000) T-Coffee: A novel method for fast and accurate multiple sequence alignment. J. Mol. Biol, . 302, 205–217[CrossRef][Web of Science][Medline].
Thompson, J.D., et al. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res, . 22, 4673–4680
Thompson, J.D., et al. (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res, . 25, 4876–4882
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