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71.
72.
Cline MS Smoot M Cerami E Kuchinsky A Landys N Workman C Christmas R Avila-Campilo I Creech M Gross B Hanspers K Isserlin R Kelley R Killcoyne S Lotia S Maere S Morris J Ono K Pavlovic V Pico AR Vailaya A Wang PL Adler A Conklin BR Hood L Kuiper M Sander C Schmulevich I Schwikowski B Warner GJ Ideker T Bader GD 《Nature protocols》2007,2(10):2366-2382
Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape. 相似文献
73.
In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). Glycosylation is by far the most diverse of the PTM processes. Natural protein production methods typically produce PTM or glycoform mixtures within which function is difficult to dissect or control. Chemical tagging methods allow the precise attachment of multiple glycosylation modifications to bacterially expressed (bare) protein scaffolds, allowing reconstitution of functionally effective mimics of glycoproteins in higher organisms. In this way combining chemical control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. This protocol describes the modification of Cys residues in proteins using glycomethanethiosulfonates and glycoselenenylsulfides and the modification of azidohomoalanine residues, introduced by Met replacement using auxotrophic Met(-) Escherichia coli strains, with glycoalkynes and the combination of these techniques for the creation of dual-tagged proteins. Each glycosylation procedure outlined in this protocol can be achieved in half a day. 相似文献
74.
Imaging mass spectrometry (IMS) allows the direct investigation of both the identity and the spatial distribution of the molecular content directly in tissue sections, single cells and many other biological surfaces. In this protocol, we present the steps required to retrieve the molecular information from tissue sections using matrix-enhanced (ME) and metal-assisted (MetA) secondary ion mass spectrometry (SIMS) as well as matrix-assisted laser desorption/ionization (MALDI) IMS. These techniques require specific sample preparation steps directed at optimal signal intensity with minimal redistribution or modification of the sample analytes. After careful sample preparation, different IMS methods offer a unique discovery tool in, for example, the investigation of (i) drug transport and uptake, (ii) biological processing steps and (iii) biomarker distributions. To extract the relevant information from the huge datasets produced by IMS, new bioinformatics approaches have been developed. The duration of the protocol is highly dependent on sample size and technique used, but on average takes approximately 5 h. 相似文献
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Davide Sala Yuanpeng Janet Huang Casey A. Cole David A. Snyder Gaohua Liu Yojiro Ishida G.V.T. Swapna Kelly P. Brock Chris Sander Krzysztof Fidelis Andriy Kryshtafovych Masayori Inouye Roberto Tejero Homayoun Valafar Antonio Rosato Gaetano T. Montelione 《Proteins》2019,87(12):1315-1332
CASP13 has investigated the impact of sparse NMR data on the accuracy of protein structure prediction. NOESY and 15N-1H residual dipolar coupling data, typical of that obtained for 15N,13C-enriched, perdeuterated proteins up to about 40 kDa, were simulated for 11 CASP13 targets ranging in size from 80 to 326 residues. For several targets, two prediction groups generated models that are more accurate than those produced using baseline methods. Real NMR data collected for a de novo designed protein were also provided to predictors, including one data set in which only backbone resonance assignments were available. Some NMR-assisted prediction groups also did very well with these data. CASP13 also assessed whether incorporation of sparse NMR data improves the accuracy of protein structure prediction relative to nonassisted regular methods. In most cases, incorporation of sparse, noisy NMR data results in models with higher accuracy. The best NMR-assisted models were also compared with the best regular predictions of any CASP13 group for the same target. For six of 13 targets, the most accurate model provided by any NMR-assisted prediction group was more accurate than the most accurate model provided by any regular prediction group; however, for the remaining seven targets, one or more regular prediction method provided a more accurate model than even the best NMR-assisted model. These results suggest a novel approach for protein structure determination, in which advanced prediction methods are first used to generate structural models, and sparse NMR data is then used to validate and/or refine these models. 相似文献
78.
Joya E. Nahon Menno Hoekstra Vanessa van Harmelen Patrick C.N. Rensen Ko Willems van Dijk Sander Kooijman Miranda Van Eck 《生物化学与生物物理学报:疾病的分子基础》2019,1865(2):494-501
Objective
Proteoglycan 4 (Prg4) has emerged from human association studies as a possible factor contributing to weight gain, dyslipidemia and insulin resistance. In the current study, we investigated the causal role of Prg4 in controlling lipid and glucose metabolism in mice.Methods
Prg4 knockout (KO) mice and wild-type (WT) littermates were challenged with an obesogenic high-fat diet (45% of total calories as fat) for 16?weeks. To further stimulate the development of metabolic alterations, 10% fructose water was provided starting from week 13.Results
Prg4 deficiency only tended to reduce diet-induced body weight gain, but significantly improved glucose handling (AUC: ?29%; p?<?0.05), which was also reflected by a tendency towards a reduced HOMA-IR score (?49%; p?=?0.06 as compared to WT mice). This coincided with lower hepatic expression of glycolysis (Gck: ?30%; p?<?0.05) and lipogenesis (Acc: ?21%; p?<?0.05 and Scd1: ?38%; p?<?0.001) genes, which translated in significantly lower hepatic triglyceride levels (?56%; p?<?0.001) in Prg4 KO mice as compared to WT mice. Prg4 KO mice likely had lower glucose utilization by skeletal muscle as compared to WT mice, judged by a significant reduction in the genes Glut4 (?29%; p?<?0.01), Pfkm (?21%; p?<?0.05) and Hk2 (?39%; p?<?0.001). Moreover, Prg4 KO mice showed a favorable white adipose tissue phenotype with lower uptake of triglyceride-derived fatty acids (?46%; p?<?0.05) and lower gene expression of inflammatory markers Cd68, Mcp1 and Tnfα (?65%, ?81% and ?63%, respectively; p?<?0.01) than WT mice.Conclusion
Prg4 KO mice are protected from high-fat diet-induced glucose intolerance and fatty liver disease. 相似文献79.
A method is presented that positions polar hydrogen atoms in protein structures by optimizing the total hydrogen bond energy. For this goal, an empirical hydrogen bond force field was derived from small molecule crystal structures. Bifurcated hydrogen bonds are taken into account. The procedure also predicts ionization states of His, Asp, and Glu residues. During optimization, sidechain conformations of His, Gln, and Asn residues are allowed to change their last χ angle by 180° to compensate for crystallographic misassignments. Crystal structure symmetry is taken into account where appropriate. The results can have significant implications for molecular dynamics simulations, protein engineering, and docking studies. The largest impact, however, is in protein structure verification: over 85% of protein structures tested can be improved by using our procedure. Proteins 26:363–376 © 1996 Wiley-Liss, Inc. 相似文献