title: MUSTANG-MR structural sieving server: applications in protein structural analysis and crystallography.
abstract: BACKGROUND
  A central tenet of structural biology is that related proteins of common function share structural similarity. This has key practical consequences for the derivation and analysis of protein structures, and is exploited by the process of "molecular sieving" whereby a common core is progressively distilled from a comparison of two or more protein structures. This paper reports a novel web server for "sieving" of protein structures, based on the multiple structural alignment program MUSTANG.
  
  
  RESULTS
  "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. To aid the identification of structurally conserved regions of functional importance in an ensemble of protein structures, Lesk-Hubbard graphs are generated, plotting the number of residue correspondences in a superposition as a function of its corresponding RMSD. The conserved "core" (or typically active site) shows a linear trend, which becomes exponential as divergent parts of the structure are included into the superposition.
  
  
  CONCLUSIONS
  The application addresses two fundamental problems in structural biology: first, the identification of common substructures among structurally related proteins--an important problem in characterization and prediction of function; second, generation of sieved models with demonstrated uses in protein crystallographic structure determination using the technique of Molecular Replacement.
authors.affiliation: NICTA Victoria Research Laboratory at The University of Melbourne, The University of Melbourne, Melbourne, Australia.
authors.forename: Arun S
authors.initials: AS
authors.lastname: Konagurthu
authors.forename: Cyril F
authors.initials: CF
authors.lastname: Reboul
authors.forename: Jason W
authors.initials: JW
authors.lastname: Schmidberger
authors.forename: James A
authors.initials: JA
authors.lastname: Irving
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Lesk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stuckey
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Buckle
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D011506:Proteins / Q000737:chemistry; D012984:Software; D040681:Structural Homology, Protein
chemical_list: D011506:Proteins
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D253-9
references.pmid: 17068077
references.citation: Methods Enzymol. 2003;374:229-44
references.pmid: 14696376
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Bioinformatics. 2004 Feb 12;20(3):426-7
references.pmid: 14960472
references.citation: Bioinformatics. 2008 Sep 15;24(18):2096-7
references.pmid: 18689808
references.citation: Proteins. 2001 Feb 15;42(3):378-82
references.pmid: 11151008
references.citation: J Mol Biol. 1992 Sep 5;227(1):197-213
references.pmid: 1522585
references.citation: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references.pmid: 15034147
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W284-8
references.pmid: 15980471
references.citation: J Mol Biol. 1995 Apr 7;247(4):536-40
references.pmid: 7723011
references.citation: Acta Crystallogr D Biol Crystallogr. 2005 Apr;61(Pt 4):458-64
references.pmid: 15805601
references.citation: Bioinformatics. 2008 Feb 1;24(3):426-7
references.pmid: 18174182
references.citation: Bioinformatics. 2008 Mar 15;24(6):872-3
references.pmid: 18227113
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Proteins. 2006 Aug 15;64(3):559-74
references.pmid: 16736488
references.citation: Protein Sci. 2006 May;15(5):1187-92
references.pmid: 16597838