ClusPro: a fully automated algorithm for protein-protein docking

Comeau, Stephen R.; Gatchell, David W.; Vajda, Sándor; Camacho, Carlos J.

doi:10.1093/nar/gkh354

Cited by 724 publications

(613 citation statements)

References 28 publications

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“…SOS DH-PH-cat (molecule B in Protein Data Bank entry 1XD4) and SOS Histone (molecule E in PDB entry 1Q9C) were docked by using the ClusPro docking server (18,19) with the DOT algorithm [without electrostatics (20)] and the present default parameters. We followed the recommended default procedure in which 20,000 models were retained after initial docking and ranked based on desolvation energies and electrostatics.…”

Section: Methodsmentioning

confidence: 99%

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Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

Sondermann

Nagar

Bar–Sagi

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The Ras-specific nucleotide exchange factor son of sevenless (SOS) is a large, multidomain protein with complex regulation, including a Ras-dependent allosteric mechanism. The N-terminal segment of SOS, the histone domain, contains two histone folds, which is highly unusual for a cytoplasmic protein. Using a combination of computational docking, small-angle x-ray scattering, mutagenesis, and calorimetry, we show that the histone domain folds into the rest of SOS and docks onto a helical linker that connects the pleckstrin-homology (PH) and Dbl-homology (DH) domains of SOS to the catalytic domain. In this model, a positively charged surface region on the histone domain is positioned so as to provide a fourth potential anchorage site on the membrane for SOS in addition to the PH domain, the allosteric Ras molecule, and the C-terminal adapter-binding site. The histone domain in SOS interacts with the helical linker, using a region of the surface that in nucleosomes is involved in histone tetramerization. Adjacent surface elements on the histone domain that correspond to the DNA-binding surface of nucleosomes form the predicted interaction site with the membrane. The orientation and position of the histone domain in the SOS model implicates it as a potential mediator of membrane-dependent activation signals.histone fold ͉ membrane interaction ͉ small-angle x-ray scattering ͉ signal transduction ͉ structure T he small G protein Ras is a cellular switch that cycles between an active GTP-bound state and an inactive GDP-bound state. GTP and GDP are both slow to dissociate from Ras, and the action of nucleotide exchange factors is critical for converting inactive Ras⅐GDP to the active Ras⅐GTP form (1). The activation of growth factor receptors in animal cell signaling results in the recruitment of the Ras-specific nucleotide exchange factor son of sevenless (SOS) to the plasma membrane, where it engages Ras and causes dissociation of bound nucleotide (2). The unregulated activation of Ras is a frequent hallmark of many cancers, a fact that underscores the importance of strict control of the nature of the nucleotide bound to Ras (3).SOS is a large protein (Ϸ1,300 residues; see Fig. 1 for a schematic diagram of its domain structure) that promotes nucleotide release by binding to Ras and opening up its active site (4). The Rem (Ras exchanger motif) and Cdc25 (named for the Ras activator protein in yeast) domains, located in the C-terminal half of SOS, are the minimal elements required for nucleotide exchange activity. The catalytic site of SOS, where nucleotide release from Ras occurs, is located entirely within the Cdc25 domain (4).We recently made the surprising discovery that Ras, which is the substrate of SOS, is itself required for SOS activity (5, 6). The binding of Ras⅐GTP to a distal site on the Cdc25 domain, bracketed by the Rem domain, stimulates nucleotide exchange activity. Perhaps more surprising was the realization that the binding of Ras⅐GDP to the distal allosteric site is required even for basal SOS activit...

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Section: Methodsmentioning

confidence: 99%

“…3B) obtained by x-ray crystallography to a docking server (ClusPro) (see Materials and Methods and ref. 18). We placed no restrictions on the possible docking modes and did not bias the calculations to consider Arg-552, Asp-140, or Asp-169 in any particular way.…”

Section: Computational Docking Of the Histone Domain Onto Sos Dh-ph-cmentioning

confidence: 99%

Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

Sondermann

Nagar

Bar–Sagi

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Based on the model of UBIAD1 (Nickerson et al, 2010) a protein-protein docking was performed with ClusPro TERE1 AND TBL2 AFFECT BLADDER CANCER CELL CHOLESTEROL(http://nrc.bu.edu/cluster/) (Comeau et al, 2004a(Comeau et al, , 2004b to investigate possible interactions between UBIAD1 and Apoliprotein E3. For this purpose the X-ray structure of the Apolipoprotein E3 22Kd Fragment Lys146Gln Mutant (PDB entry 1H7I) (Rupp et al, to be published) was used.…”

Section: Molecular Modelingmentioning

confidence: 99%

The Bladder Tumor Suppressor Protein TERE1 (UBIAD1)Modulates Cell Cholesterol: Implications for Tumor Progression

Fredericks

McGarvey

Wang

et al. 2011

DNA and Cell Biology

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Convergent evidence implicates the TERE1 protein in human bladder tumor progression and lipid metabolism. Previously, reduced TERE1 expression was found in invasive urologic cancers and inhibited cell growth upon re-expression. A role in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural TERE1 mutations associate with Schnyder's corneal dystrophy, characterized by lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2 dosage via ectopic expression and interfering RNA and measured cholesterol by Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were evaluated by binding assays and molecular modeling. We conducted a bladder tumor microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1 point mutations affected APOE interactions, and resulted in cholesterol levels that differed from wild type. Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression.

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“…ClusPro 2.0 server [21] was used to dock RPL model to candidate partners. RPL model was input as receptor and candidate partners as ligand.…”

Section: Protein-protein Interaction Predictionmentioning

confidence: 99%

Bioinformatics Analysis of the Ribosomal Proteins,RPL27, RPL37a and RPL41: 3-D Protein Modeling and Protein-protein Interaction Prediction

Chan¹,

Sim²

2013

IJBBB

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Abstract-Ribosomal proteins (RPs) are constituents of ribosome important for protein biosynthesis but likely to have extraribosomal functions. Many RPs are associated with various diseases and cancers. A previous study reported RPL27, RPL37a and RPL41 gene to be downregulated in nasopharyngeal carcinoma (NPC) derived cell lines compared to their normal counterpart. However, their actual physiological roles in organogenesis or tumorigenesis have not been properly defined. In this paper, we report on the findings of structural prediction of these three genes and infer their interactions with other proteins using structural neighbor prediction and molecular docking strategies. Our results revealed that RPL27 interact with SYNJ2 and UBC9. RPL27 is predicted to mediate RNA binding protein and deregulate sumolyation. RPL37a is suggested to interact with CTNNB1, SCMH1 and ATBF1. It is predicted to deregulate Wnt degradation pathway, inhibit β-catenin migration and regulate homeotic transcription. Our studies on RPL41 did not allow logical inference on possible interacting factors. Nevertheless, results on RPL27 and RPL37a provide rational data for the elucidation of their molecular activities.Index Terms-Protein modeling, extraribosomal functions, protein-protein interaction prediction, ribosomal protein.

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ClusPro: a fully automated algorithm for protein-protein docking

Cited by 724 publications

References 28 publications

Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

The Bladder Tumor Suppressor Protein TERE1 (UBIAD1)Modulates Cell Cholesterol: Implications for Tumor Progression

Bioinformatics Analysis of the Ribosomal Proteins,RPL27, RPL37a and RPL41: 3-D Protein Modeling and Protein-protein Interaction Prediction

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