From Protein Structure to Function with Bioinformatics.pdf

200 E.C. Meng et al.Table 8.2 Web sites for 3D motif software downloadName and URL Description DownloadsNestor3Dstaffnet.kingston.ac.uk/∼ku33185/Nestor3D.htmlPAR-3Dsunserver.cdfd.org.in:8080/protease/PAR_3DUppsala Software Factoryalpha2.bmc.uu.se/usfNestor3D generates a consensusmotif given inputstructures and specificationof how to superimposethem.PAR-3D compares a structureto distance and angleranges for predefinedmotifs.SPASM compares a userdefined3D motif to adatabase of structures,RIGOR compares a querystructure to a database of3D motifs.Nestor3D Java jar filesrequiring Java 1.5 or later,tested only on WindowsPAR-3D Perl scripts andgeometric descriptions of6 protease motifs, 10 glycolyticpathway enzymemotifs, and 2 metal-bindingsite motifsSPASM and RIGOR executablesfor Unix-based platformsincluding Mac OSX; SPASM- and RIGORsearchabledatabases.RIGOR database contains73,164 motifs from individualstructures, 57,719labelled with residue typeand 15,445 unlabelled(“engineerable”)Motifs based on individual structures identified superfamily members with greatersensitivity and specificity than a consensus motif, suggesting that averaging coordinatesmay not be helpful when the structures are highly divergent.The Match Augmentation algorithm performs a prioritized search, starting withseed matches of the three highest-ranked residues in a 3D motif and incorporatingprogressively lower-ranked residues, to return any matches with RMSD values belowa cutoff (Chen et al. 2005). Residues were represented by their alpha-carbons , labelledwith residue type, and ranked by evolutionary importance inferred from sequencealignments (Kristensen et al. 2006), although a different ranking method could havebeen used. Prioritization decreases the search space, and performance is furtherenhanced by efficient distance comparisons. Augmentation (expanding a match) proceedsby a stack-based depth-first search. Finally, statistical significance is assessedwith a nonparametric model based on the distribution of RMSD values when themotif is compared to a sample of chains from the PDB. Random samples of only 5%were found sufficient for this purpose (Chen et al. 2005). For five- to eight-pointmotifs representing isofunctional families (members of which catalyze the identicalreaction), averaged motif coordinates were shown to provide sensitivity similar to thatof the most sensitive single-structure motifs and specificity similar to the averagespecificity of the single-structure motifs (Chen et al. 2007b).