Protein function prediction using the Protein Link EXplorer (PLEX)

Date, Shailesh V.; Marcotte, Edward M.

doi:10.1093/bioinformatics/bti313

Cited by 40 publications

(34 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phylogenetic and evolutionary methods for detecting sequence similarity model the changes in protein sequences assuming their divergence from each other during evolution. Some methods include evolutionary traces [21][22][23] and comparative genomics [24] methods such as Clusters of Orthologous Groups [25], gene co-evolution [26], and cross-species co-occurrence [27].…”

Section: Annotation Methods Based On Sequence Similaritymentioning

confidence: 99%

Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development

Bandyopadhyay

Huan

Prins

et al. 2009

J Comput Aided Mol Des

View full text Add to dashboard Cite

Protein function prediction is one of the central problems in computational biology. We present a novel automated protein structure-based function prediction method using libraries of local residue packing patterns that are common to most proteins in a known functional family. Critical to this approach is the representation of a protein structure as a graph where residue vertices (residue name used as a vertex label) are connected by geometrical proximity edges. The approach employs two steps. First, it uses a fast subgraph mining algorithm to find all occurrences of family-specific labeled subgraphs for all well characterized protein structural and functional families. Second, it queries a new structure for occurrences of a set of motifs characteristic of a known family, using a graph index to speed up Ullman's subgraph isomorphism algorithm. The confidence of function inference from structure depends on the number of family-specific motifs found in the query structure compared with their distribution in a large non-redundant database of proteins. This method can assign a new structure to a specific functional family in cases where sequence alignments, sequence patterns, structural superposition and active site templates fail to provide accurate annotation.

show abstract

Section: Annotation Methods Based On Sequence Similaritymentioning

confidence: 99%

Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development

Bandyopadhyay

Huan

Prins

et al. 2009

J Comput Aided Mol Des

View full text Add to dashboard Cite

show abstract

“…The genomes of organisms containing (Methanococcus jannaschi, Homo sapiens, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Arabidopsis thaliana) or lacking (Drosophila melanogaster, Escherichia coli, and Bacillus subtilis) the wyosine modification were analyzed using the comparative genomics platform, Protein Link Explorer (PLEX) (43). A BLAST E-value of 10 Ϫ10 was set as a threshold for gene identification.…”

Section: Methodsmentioning

confidence: 99%

Discovery of a Gene Family Critical to Wyosine Base Formation in a Subset of Phenylalanine-specific Transfer RNAs

Waas

Crécy‐Lagard

Schimmel

2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

In all organisms, the functions of tRNAs in translation are enhanced by a series of post-transcriptional modifications (4). Over 80 modifications are known, and their presence vastly expands the structural and chemical diversity of native tRNA (2). (In a putative RNA world, base modifications may have provided a way to diversify the chemical and structural properties of RNAs.) The modification-dependent structural stability and function correlate with increased cellular fitness and viability (5, 9). The importance of these modifications is underscored by a large investment of resources for their biosynthesis, with estimates suggesting nearly 1% of some bacterial genomes being dedicated to tRNA modification genes (4).Wyebutosine (yW) 3 of yeast phenylalanine-specific tRNA (tRNA Phe )was one of the earliest tRNA modifications to be discovered (10 -14).Wyebutosine is a fluorescent, tricyclic base and a member of the wyosine family of hypermodified guanosines. All wyosine bases (Ybs) are characterized by a 1H-imidazo[1,2-␣]purine core structure and a strict occurrence in archaeal and eukaryal tRNA Phe ( Figs. 1 and 2). Wyosine bases, isolated from different organisms, show variations in ring methylation and side chain structure (15)(16)(17)(18)(19)(20). Generally, archaeal Yb structures are less differentiated then their eukaryotic counterparts.The hydrophobic nature of yW 37 promotes stacking with adjacent bases (A 36 and A 38 ) and restricts the conformational flexibility of the anticodon (21-25). Removal of yW produced local changes in anticodon conformation, as well as long range perturbations in tRNA Phe tertiary structure (26). These structural changes were accompanied by subtle differences in codon specificity 4 and a modest increase in retroviral ribosomal frameshifting (determined in cell-free extract) (27-29). Most interesting, the tRNA Phe from mouse neuroblastoma cell lacked Yb but was more efficient than the fully modified tRNA Phe in a cell-free translation system (30 -32). Although it is unclear if hypomodified tRNAs contribute to tumor-specific properties, these tRNAs support the high levels of translation required by rapidly dividing cells. Thus, despite a good understanding of its role in maintaining anticodon structure, the function of yW in translation is unclear.Although the biosynthesis of wyebutosine has been partially characterized, the genes involved are largely unknown. Several structural components of yW were identified by metabolic labeling experiments. The purine substructure was shown as being derived from the coded guanosine (33,34). NMR studies of 13 C-enriched tRNA Phe implicated the methyl group of methionine as a source for carbon-10 (refer to Fig. 1 for numbering), and for the side chain ester and N 3 -methyl moieties (35). Conflicting evidence obscures understanding the origin of the 3-amino-3-carboxypropyl side chain (36, 37). The in vivo kinetics of Yb biosynthesis of Xenopus laevis were investigated (34). By using the sitespecifically labeled [ 32 P]tRNA Phe transcript in X. ...

show abstract

“…In the wake of genomic era (Kanehisa and Bork, 2003) many attempts at function annotation that employ multiple data types and statistical frameworks for their integration are underway and have proved to be highly successful in annotating prokaryotic genomes (Date and Marcotte, 2005;von Mering et al, 2005). These frameworks output profiles or clusters of genes and their interpretation is largely dependent on expert knowledge.…”

Section: Introductionmentioning

confidence: 99%

Enhanced function annotations for Drosophila serine proteases: A case study for systematic annotation of multi-member gene families

Shah

Tripathi

Jensen

et al. 2008

Gene

View full text Add to dashboard Cite

Protein function prediction using the Protein Link EXplorer (PLEX)

Abstract: http://bioinformatics.icmb.utexas.edu/plex

Cited by 40 publications

References 9 publications

Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development

Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development

Discovery of a Gene Family Critical to Wyosine Base Formation in a Subset of Phenylalanine-specific Transfer RNAs

Enhanced function annotations for Drosophila serine proteases: A case study for systematic annotation of multi-member gene families

Contact Info

Product

Resources

About