Structural Sieving Server

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This server uses the structural alignment program MUSTANG to structurally align multiple protein structures. The server will also remove residues from the alignment that are below a threshold root mean square deviation (RMSD), producing "sieved" models. These are of practical use in characterizing conformational change (eg conserved core residues) and in producing multiple alternative search models for X-ray crystal structure determination using Molecular Replacement.

Methods

MUSTANG-MR web server benefits from an intuitive interface to MUSTANG (Konagurthu, et al., 2006) and a specially designed sieving procedure. “Sieved” models are generated from MUSTANG generated multiple alignment and superpositions by iteratively filtering out noisy residue-residue correspondences, until the resultant correspondences in the models are optimally ‘superposable’ under a threshold of RMSD. This residue-level sieving is also accompanied by iterative elimination of the poorly-fitting structures from the input ensemble. Therefore, by varying the thresholds of RMSD and the cardinality of the ensemble, multiple sieved models are generated for a given multiple alignment and superposition from MUSTANG.

MUSTANG-MR is a project fork on MUSTANG with sieving incorporated into it. MUSTANG-MR is implemented in C++ and is available under an open-source license. A user-friendly web interface is written in JSP/Java. Figure 1 illustrates the working of the sieving server. Multiple PDB files can be uploaded and processed rapidly. The server through its excellent interface allows direct visual analysis of the results by giving access to a range of automated tools. Exhaustively sieved models can be displayed interactively. Graphical representations of alignments and superpositions of sieved structures are provided using Jmol, Jalview and BioJava. Superimposed structural coordinates and residue-level alignment can be accessed in PDB and FASTA formats.

To aid the identification of structurally conserved regions of functional importance in an ensemble of protein structures, Lesk-Hubbard graphs (Irving, et al., 2001) are generated, plotting the number of residue correspondences (NCore) in a superposition as a function of its corresponding RMSD. The conserved “core” shows a linear trend, which becomes exponential as divergent parts of the structure are included into the superposition.

Links

Mustang: Arun Konagurthu home page provides an archive containing the latest source and test data, along with help and installation instruction.

Buckle Structural Bioinformatics Group

Whisstock Lab

References

Cite: MUSTANG-MR Structural Sieving Server: Applications in Protein Structural Analysis and Crystallography, Konagurthu AS, Reboul CF, Schmidberger JS, Irving, JA, Lesk AM, Stuckey PJ, Whisstock JC, and Buckle AM (2010) MUSTANG-MR Structural Sieving Server: Applications in Protein Structural Analysis and Crystallography. PLoS One. Apr 6;5(4):e10048. WebLink

MUSTANG: A multiple structural alignment algorithm, Arun S. Konagurthu, James C. Whisstock, Peter J. Stuckey, Arthur M. Lesk, Proteins: Structure, Function, and Bioinformatics, 2006, Volume 64, Issue 3 , Pages 559 - 574.

Mustang-MR Server has been developped using:
Jmol: Java viewer for chemical structures in 3D.
Biojava: Project dedicated to providing a Java framework for processing biological data.
Jalview: multiple alignment editor.
JFreeChart: Java chart library.

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