The ClusPro web server for protein–protein docking

Kozakov, Dima; Hall, David R.; Xia, Bing; Porter, Kathryn A.; Padhorny, Dzmitry; Yueh, Christine; Beglov, Dmitri; Vajda, Sándor

doi:10.1038/nprot.2016.169

Cited by 2,400 publications

(1,935 citation statements)

References 134 publications

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“…The VWF‐A2 domain was modeled with CPH model 3.2 server (www.cbs.dtu.dk) that used the solved crystal structure of the VWF‐A2 domain (3ZQK.A) as a template 12. The complex structure was obtained using protein‐protein docking server ClusPro2.0 (http://cluspro.bu.edu)13 and PatchDock‐server (http://bioinfo3d.cs.tau.ac.il/PatchDock)14 (Figure 1). The ClusPro prediction was preferred over Patchdock prediction as the PDBsum Procheck (http://www.ebi.ac.uk)15 values were less favorable for the latter.…”

Section: Methodsmentioning

confidence: 99%

Combined effects of two mutations in von Willebrand disease 2M phenotype

Woods

Paiva

Kempfer

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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Essentials Compound heterozygosity causes a VWD2M phenotype in a child with severe bleeding symptoms.p.P1648fs*45 changes the folding of A2 domain altering VWF binding to GPIbα and type VI collagen.p.P1648fs*45 was considered as an apparent de novo mutation; AS‐PCR revealed paternal mosaicism.Bleeding score and DDAVP's response were worse than those seen in VWD2M heterozygous controls. BackgroundType 2M von Willebrand disease (VWD2M) is usually characterized by VWF:RCo/VWF:Ag<0.6 and normal multimeric profile; desmopressin (DDAVP) challenge test commonly shows poor response of VWF:RCo.ObjectiveWe describe the bleeding tendency and the laboratory phenotype in a patient carrying two heterozygous mutations affecting VWF‐A1 domain and VWF‐A2 domain.Subjects/methodsA 12‐year‐old patient (O blood group) with severe hemorrhagic tendency was phenotypically and genotypically analyzed; his parents were also studied.ResultsThe proband showed decrease FVIII:C, VWF:RCo/VWF:Ag, and VWF:CB6/VWF:Ag ratios, but normal platelet count, VWF:CB1/VWF:Ag ratio, VWFpp and multimeric pattern, suggesting a VWD2M phenotype. The DDAVP challenge test, compared to controls (VWD2M patients with mutations in VWF‐A1 domain), showed lower increase of FVIII:C and VWF:Ag than in heterozygous, but very similar to homozygous control. Two mutations were found in heterozygous and trans presentation: p.Pro1648fs*45 and a novel missense mutation, p.Arg1426Cys. The mother was p.Arg1426Cys heterozygous carrier, with few clinical symptoms. The father was asymptomatic, with no mutations. The p.Pro1648fs*45 was considered an apparent de novo mutation; proband's AS‐PCR revealed mosaicism in the paternal allele. According to the predicted models, p.Arg1426Cys would not be affecting the binding of GPIbα to A1 domain, whereas p.Pro1648fs*45 seems to modify the folding of A2 domain, and in this way, it would affect the binding to GPIbα and type VI collagen. We believe that the combination of these two heterozygous mutations, in a child with O blood group, could result in a defective phenotype enhancer.

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Section: Methodsmentioning

confidence: 99%

Combined effects of two mutations in von Willebrand disease 2M phenotype

Woods

Paiva

Kempfer

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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“…Here, repulsive, attractive, electrostatic as well as interactions extracted from the decoys as the reference state, are considered for structure-based pairwise potential calculation in docking. 25 Visualization of docking structures with USCF Chimera, 22 helps to calculate the distances and torsional angle distortion of binding, with IgE and FcεRI receptor in presence of four procyanidin molecules. The positions of four surface -exposed tryptophan's (W110, W113, W156 and W87) molecules which are responsible for α subunit of FcεRI receptor binding with IgE molecules with high affinity, are distorted due to presence of procyanidin molecule.…”

Section: And 3d Structures Of Procyanidin B1 B2 C1 and C2mentioning

confidence: 99%

“…21 MOL SDF format of these ligands are converted to mol2 file using UCSF Chimera tool. 22 Molecular docking study Molecular docking is a computational method, which forecasts the preferred positioning of two protein molecules e.g.IgE and FcεRI receptor when bound to each other and form a stable complex using ClusPro 2.2 server. 23 Docking study is also used here to investigate the binding affinity of IgE and FcεRI receptor in presence of four small molecules e.g.…”

Section: And 3d Structures Of Procyanidin B1 B2 C1 and C2mentioning

confidence: 99%

Immunoinformatics Study of Procyanidins as Mast Cell Stabilizers

Basu¹,

Sarkar

Basak

2018

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Background:Allergens are foreign proteins that stimulate the production of immunoglobulin E (IgE), when they come in contact with human body. These allergens after binding with IgE through FcεRI receptor, triggers the signal transduction reaction in mast cell and basophil cells, leading to allergic reactions by releasing some mediators. Mast cell stabilizer block mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine 8 and related mediators e.g. leukotrienes (for basophils) and prostaglandin D2 and IL-5 (for mast cells) during hypersensitivity reaction. Though innumerable synthetic mast cell stabilizers are present 9 in our medicinal science, but the search for suitable natural product as mast cell stabilizer is still going on. 10 Comparative study shows that higher efficiency for natural product quercetin than synthetic compound cromolyn for inhibiting allergic reactions.11 Several inhibitors of IgE:FcεRI binding have been identified e.g. an anti-IgE therapeutic antibody (omalizumab) , an engineered protein inhibitor, DARPin E2_799-11, which are used to treat severe allergic asthma. 12,13 Polyphenols which are abundant in apple are proven effective for allergic rhinitis treatment by preventing degranulation of granulocytes in mast cells. 14,15,16 Procyanidins are polymeric form of catechins. In apple, almost 50% to 60% polyphenols are oligomers and polymers of catechins.Dimeric catechins are procyanidin B1, B2, C1 present in apple extract shows antiallergic activity on rhinitis treatment. Among them, procyanidin C1 extracted from unripe apples (Rosaceae mal- 815 lus) shows anti-allergic effect by various mechanisms e.g. FcεRI induced degranulation and cytokine production of mast cells. Procyanidin C1 which is related with intra-cellular signalling pathway,prevents FcεRI-mediated mast cell activation. 17 The flow cytometric study is confirmed that polymeric procyanidins supress the binding of IgE antibody to FcεRI.17 But the molecular mechanism for inhibitory effect on antibody IgE with FcεRI binding is unknown to all. A compound must have an anti-allergic activity if it inhibits the binding between Ig E antibody and FcεRI receptor during type I hypersensitivity reaction. Comparative studies on different procyanidins structures and physicochemical properties using computational methods will help us to identify apple extract, as herbal medicine in allergic reactions. Computational docking studies are used to elaborate the mechanism of action of various natural products e.g. quercetin glycosides as inhibitor of angiotensinconverting enzyme for the treatment of myocardial infarction 18 and fatty acids of black cumin oil as inhibitors of P-glycoprotein to improve pharmaceutics of many lifesaving drugs. 19 MATERIALS AND METHODS X-ray crystallographic structures for human IgE, FcεRIreceptorThe three-dimensional structure of IgE (PDBID 4J4P) and FcεRI receptor (PDBID 1F2Q) are downloaded from the RCSB protein Data Bank. 20 2D and 3D structures of procyanidin B1, B2, C1 an...

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“…ClusPro server (https://cluspro.org) was used for protein-protein docking [11] of different MAPKs and the scores were recorded in the form of lower energy expressed in Kcal/mol. The ClusPro server is a widely used tool for proteinprotein-docking analysis.…”

Section: Molecular Dockingmentioning

confidence: 99%

Untitled

2018

Bioinformation

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Abstract:Phytoalexins are small antimicrobial molecules synthesized and accumulated by plants upon exposure to pathogens. Camalexin is an indole-derived phytoalexin, which is accumulated in plants including Arabidopsis thaliana, and other Brassicaceae, which plays a major role in disease resistance against fungal pathogens. The productivity of Brassica crops is adversely affected by Alternaria blight disease, which is caused by Alternaria brassicae. In Arabidopsis thaliana, MAP kinase signalling cascade is known to be involved in synthesis of camalexin, which contributes to disease resistance against a necrtrophic fungal pathogen, Botrytis cinerea. In the present study, MAPK signalling cascade leading to biosynthesis of camalexin that triggers defense responses in B. rapa upon exposure to the most devastating nectrophic fungus, Alternaria brassicae has been elucidated with the help of previously reported MAPK cascade in Arabidopsis thaliana, Molecular modelling, docking, and protein-protein interaction analysis of MAP kinases retrieved from Brassica rapa genome have been carried out to reveal the above cascade. The tertiary structure prediction of MAPKs obtained through molecular modelling revealed that all the protein models fulfil the criteria of being the stable structures. The molecular docking of predicted models for elucidating potential partners of MAPKs revealed strong interactions between MKK1, MKK4, MKK5, MAPK3 and MAPK6 with MKK9. The MAPK signalling cascade also shows different genes that express and play major role in camalexin biosynthesis in B. rapa during defense response to A. brassicae. The understanding of MAPK defense signaling pathway in B. rapa against devastating fungal pathogen Alternaria brassicae would help in devising strategies to develop disease resistance in Brassica crops.

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The ClusPro web server for protein–protein docking

Cited by 2,400 publications

References 134 publications

Combined effects of two mutations in von Willebrand disease 2M phenotype

Combined effects of two mutations in von Willebrand disease 2M phenotype

Immunoinformatics Study of Procyanidins as Mast Cell Stabilizers

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