Protein level predictions 3 - Conservation analysis

Good way to detect information about positional sequence conservation is to visualize MSAs. This subgroup of tools consist of programs visualizing the MSAs, calculating conservation indices for each position in the alignment and color-coding the aligment for different level of sequence conservation (Thusberg et al). Group also contains tools which do the color-coding for protein-structures or based on physicochemical properties.

Programs available

• ClustalX
• ConSeq
• ConSSeq
• ConSurf
• Jalview
• MatrixPlot
• MultiDisp
• Mutationassessor.org (xvar)
• ProCon

An extensive overview of tools predicting protein level changes can be found from the recent review  article by Thusberg and Vihinen. Click here to return to the main page of protein prediction tools.

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Description of programs

ClustalX

website: ClustalX

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Reference: Larkin et al. Clustal W and Clustal X version 2.0. Bioinformatics, 2007, 23, 21, 2947-2948. doi:10.1093/bioinformatics/btm404

ConSeq

website: ConSeq

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Reference: Berezin et al. ConSeq: the identification of functionally and structurally important residues in protein sequences. Bioinformatics, 2004, 20, 8, 1322-1324. doi: 10.1093/bioinformatics/bth070

ConSSeq

website: ConSSeq

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Reference: Higa et al. ConSSeq: a web-based application for analysis of amino acid conservation based on HSSP database and within context of structure. Bioinformatics, 2004, 20, 12, 1983-1985. doi: 10.1093/bioinformatics/bth185

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ConSurf

Consurf color-codes protein structures and makes it possible for a user to view the structure color-coded based on the level of conservation of individual residues.

website: ConSurf

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References:

• Glaser et al.ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics, 2003, 19, 1, 163-164. http://bioinformatics.oxfordjournals.org/cgi/reprint/19/1/163

• Landau et al. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res., 2005, 33, Web Server issue, W299-302. doi: 10.1093/nar/gki370

Jalview

website: Jalview

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Reference: Clamp et al. The Jalview Java alignment editor. Bioinformatics, 2004, 20, 3, 426-427. doi:10.1093/bioinformatics/btg430

MatrixPlot

MatrixPlot is a tool for generating mutual information plots for sequence alignments.

website: MatrixPlot

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Reference: Gorodkin et al. MatrixPlot: visualizing sequence constraints. Bioinformatics, 1999, 15, 9, 769-770. http://bioinformatics.oxfordjournals.org/cgi/reprint/15/9/769

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MultiDisp

MultiDisp is a tool which visualizes the sequence alignment so that the height of the characters at each position reflects the frequence of amino acid at that position of  the alignment and the colour of the characters reflects the chemical nature of the amino acids.

website: MultiDisp

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Reference: Riikonen and Vihinen.

Mutationassessor.org(xvar)

Mutationassessor predicts the functional impact of amino-acid substitutions in proteins. This is done based on evolutionary conservation of the affected amino acid in protein homologs.   

website: mutationassessor.org

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Reference: 

ProCon

ProCon calculates the mutual information between pairs of sites in the multiple sequence alignment and after that build covariant networks of amino acids.

website:

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Reference: Shen and Vihinen. Conservation and covariance in PH domain sequences: physicochemical profile and information theoretical analysis of XLA-causing mutations in the Btk PH domain. Protein Eng.Des.Sel., 2004, 17, 3, 267-276. doi:10.1093/protein/gzh030

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Useful databases

• PFAM (ready-made sequence alignments)

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Review articles

• Janita Thusberg and Mauno Vihinen. Pathogenic or Not? And If So, Then How? Studying the Effects of Missense Mutations Using Bioinformatics Methods. Hum Mutat. 2009 May;30(5):703-14: doi:10.1002/humu.20938

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Other articles

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Useful Links

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