Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jul;35(Web Server issue):W653-8.
doi: 10.1093/nar/gkm293. Epub 2007 May 21.

COMPASS Server for Remote Homology Inference

Affiliations
Free PMC article

COMPASS Server for Remote Homology Inference

Ruslan I Sadreyev et al. Nucleic Acids Res. .
Free PMC article

Abstract

COMPASS is a method for homology detection and local alignment construction based on the comparison of multiple sequence alignments (MSAs). The method derives numerical profiles from given MSAs, constructs local profile-profile alignments and analytically estimates E-values for the detected similarities. Until now, COMPASS was only available for download and local installation. Here, we present a new web server featuring the latest version of COMPASS, which provides (i) increased sensitivity and selectivity of homology detection; (ii) longer, more complete alignments; and (iii) faster computational speed. After submission of the query MSA or single sequence, the server performs searches versus a user-specified database. The server includes detailed and intuitive control of the search parameters. A flexible output format, structured similarly to BLAST and PSI-BLAST, provides an easy way to read and analyze the detected profile similarities. Brief help sections are available for all input parameters and output options, along with detailed documentation. To illustrate the value of this tool for protein structure-functional prediction, we present two examples of detecting distant homologs for uncharacterized protein families. Available at http://prodata.swmed.edu/compass.

Figures

Figure 1.
Figure 1.
(A) Front page of the COMPASS server. The main section allows the user to submit the query (by pasting in the window or by specifying the file), to choose the search database, and (if needed) to enter the email address to receive the results. The section of input processing options allows the user to choose whether a PSI-BLAST run is needed to enrich the query profile with additional sequence homologs and to define the parameters of profile construction. The section of search options can be used to adjust the main parameters of the search. The section of output options allows for flexible formatting of the search results. A brief explanation of each option is available by clicking on the option's name. Additional sections include the links to more detailed documentation and to the FTP page with standalone COMPASS package. (B) Search results for uncharacterized PFAM DUF185 as a query, supporting the structure and function prediction for this family. The list of hits among SCOP domains consistently includes members of the same superfamily of S-adenosyl-l-methionine-dependent methyltransferases (SAM-Mtases) (c.66.1). (C) Example of profile-profile alignment. The header includes brief information about the hit: database identifier, protein description, full length of the MSA (‘length’), the length of the profile after purging positions with high gap content (‘filtered length’), effective number of sequences as a characteristic of sequence divergence within MSA (‘Nef f ’), followed by COMPASS score and E-value. In this example, the top and consensus sequences for compared profiles are displayed. Position matches with positive scores are marked by ‘+’, identical residues in the two consensus sequences are marked by the residue symbol. Invariant glutamates of Motifs I and II (39) involved in ligand binding are marked with red dots, glycine-rich motif is circled. D: A recently solved structure for a member of DUF185 family (PDB ID 1zkd) confirms our prediction. Side chains of the invariant glutamate residues are shown in red, glycine-rich loop is circled.
Figure 2.
Figure 2.
Search results for PFAM DUF519 suggest that this family possesses the structural fold of SAM-Mtases. (A) DUF519 is used as a query for the COMPASS search against the databases of PSI-BLAST alignments (iteration 3) for SCOP representatives. The COMPASS alignment between the query and the detected homolog (domain 1qyrA) includes characteristic motifs of the SAM-Mtase superfamily. In this example, only consensus sequences are displayed. Positions corresponding to the conserved acidic residues of Motifs I and II (39) are marked with red dots. The region of the SAM-binding loop is circled. (B) Multiple alignment including representatives from DUF519 (top) and 1qyrA homologs (bottom). Sequences are denoted by NCBI GI numbers. Positions corresponding to conserved acidic residues of SAM-Mtase are marked with red dots. The region of the ligand-binding loop is marked with a line. Invariant residues are boxed in black. Uncharged residues (all amino acids except D, E, K, R) in mostly hydrophobic sites are highlighted in yellow; non-hydrophobic residues (all amino acids except W, F, Y, M, L, I, V) at mostly hydrophilic sites are highlighted in light gray. The secondary structure of 1qyrA is shown below the alignment, with α-helices and β-strands displayed as cylinders and arrows, respectively.

Similar articles

See all similar articles

Cited by 17 articles

See all "Cited by" articles

References

    1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–3402. - PMC - PubMed
    1. Schaffer AA, Aravind L, Madden TL, Shavirin S, Spouge JL, Wolf YI, Koonin EV, Altschul SF. Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. Nucleic Acids Res. 2001;29:2994–3005. - PMC - PubMed
    1. Eddy SR. Profile hidden Markov models. Bioinformatics. 1998;14:755–763. - PubMed
    1. Karplus K, Barrett C, Cline M, Diekhans M, Grate L, Hughey R. Predicting protein structure using only sequence information. Proteins. 1999;37(Suppl. 3):121–125. - PubMed
    1. Karplus K, Karchin R, Draper J, Casper J, Mandel-Gutfreund Y, Diekhans M, Hughey R. Combining local-structure, fold-recognition, and new fold methods for protein structure prediction. Proteins. 2003;53(Suppl. 6):491–496. - PubMed

Publication types

Feedback