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41.
Toward rational protein crystallization: A Web server for the design of crystallizable protein variants 总被引:1,自引:0,他引:1
Goldschmidt L Cooper DR Derewenda ZS Eisenberg D 《Protein science : a publication of the Protein Society》2007,16(8):1569-1576
Growing well-diffracting crystals constitutes a serious bottleneck in structural biology. A recently proposed crystallization methodology for "stubborn crystallizers" is to engineer surface sequence variants designed to form intermolecular contacts that could support a crystal lattice. This approach relies on the concept of surface entropy reduction (SER), i.e., the replacement of clusters of flexible, solvent-exposed residues with residues with lower conformational entropy. This strategy minimizes the loss of conformational entropy upon crystallization and renders crystallization thermodynamically favorable. The method has been successfully used to crystallize more than 15 novel proteins, all stubborn crystallizers. But the choice of suitable sites for mutagenesis is not trivial. Herein, we announce a Web server, the surface entropy reduction prediction server (SERp server), designed to identify mutations that may facilitate crystallization. Suggested mutations are predicted based on an algorithm incorporating a conformational entropy profile, a secondary structure prediction, and sequence conservation. Minor considerations include the nature of flanking residues and gaps between mutation candidates. While designed to be used with default values, the server has many user-controlled parameters allowing for considerable flexibility. Within, we discuss (1) the methodology of the server, (2) how to interpret the results, and (3) factors that must be considered when selecting mutations. We also attempt to benchmark the server by comparing the server's predictions with successful SER structures. In most cases, the structure yielding mutations were easily identified by the SERp server. The server can be accessed at http://www.doe-mbi.ucla.edu/Services/SER. 相似文献
42.
Antoniewicz MR Kraynie DF Laffend LA González-Lergier J Kelleher JK Stephanopoulos G 《Metabolic engineering》2007,9(3):277-292
Metabolic fluxes estimated from stable-isotope studies provide a key to understanding cell physiology and regulation of metabolism. A limitation of the classical method for metabolic flux analysis (MFA) is the requirement for isotopic steady state. To extend the scope of flux determination from stationary to nonstationary systems, we present a novel modeling strategy that combines key ideas from isotopomer spectral analysis (ISA) and stationary MFA. Isotopic transients of the precursor pool and the sampled products are described by two parameters, D and G parameters, respectively, which are incorporated into the flux model. The G value is the fraction of labeled product in the sample, and the D value is the fractional contribution of the feed for the production of labeled products. We illustrate the novel modeling strategy with a nonstationary system that closely resembles industrial production conditions, i.e. fed-batch fermentation of Escherichia coli that produces 1,3-propanediol (PDO). Metabolic fluxes and the D and G parameters were estimated by fitting labeling distributions of biomass amino acids measured by GC/MS to a model of E. coli metabolism. We obtained highly consistent fits from the data with 82 redundant measurements. Metabolic fluxes were estimated for 20 time points during course of the fermentation. As such we established, for the first time, detailed time profiles of in vivo fluxes. We found that intracellular fluxes changed significantly during the fed-batch. The intracellular flux associated with PDO pathway increased by 10%. Concurrently, we observed a decrease in the split ratio between glycolysis and pentose phosphate pathway from 70/30 to 50/50 as a function of time. The TCA cycle flux, on the other hand, remained constant throughout the fermentation. Furthermore, our flux results provided additional insight in support of the assumed genotype of the organism. 相似文献
43.
Orchard S Salwinski L Kerrien S Montecchi-Palazzi L Oesterheld M Stümpflen V Ceol A Chatr-aryamontri A Armstrong J Woollard P Salama JJ Moore S Wojcik J Bader GD Vidal M Cusick ME Gerstein M Gavin AC Superti-Furga G Greenblatt J Bader J Uetz P Tyers M Legrain P Fields S Mulder N Gilson M Niepmann M Burgoon L De Las Rivas J Prieto C Perreau VM Hogue C Mewes HW Apweiler R Xenarios I Eisenberg D Cesareni G Hermjakob H 《Nature biotechnology》2007,25(8):894-898
A wealth of molecular interaction data is available in the literature, ranging from large-scale datasets to a single interaction confirmed by several different techniques. These data are all too often reported either as free text or in tables of variable format, and are often missing key pieces of information essential for a full understanding of the experiment. Here we propose MIMIx, the minimum information required for reporting a molecular interaction experiment. Adherence to these reporting guidelines will result in publications of increased clarity and usefulness to the scientific community and will support the rapid, systematic capture of molecular interaction data in public databases, thereby improving access to valuable interaction data. 相似文献
44.
The MiSink Plugin converts Cytoscape, an open-source bioinformatics platform for network visualization, to a graphical interface for the database of interacting proteins (DIP: http://dip.doe-mbi.ucla.edu). Seamless integration is possible by providing bi-directional communication between Cytoscape and any Web site supplying data in XML or tab-delimited format. Availability: MiSink is freely available for download at http://dip.doe-mbi.ucla.edu/Software.cgi. 相似文献
45.
MOTIVATION: The number of protein families has been estimated to be as small as 1000. Recent study shows that the growth in discovery of novel structures that are deposited into PDB and the related rate of increase of SCOP categories are slowing down. This indicates that the protein structure space will be soon covered and thus we may be able to derive most of remaining structures by using the known folding patterns. Present tertiary structure prediction methods behave well when a homologous structure is predicted, but give poorer results when no homologous templates are available. At the same time, some proteins that share twilight-zone sequence identity can form similar folds. Therefore, determination of structural similarity without sequence similarity would be beneficial for prediction of tertiary structures. RESULTS: The proposed PFRES method for automated protein fold classification from low identity (<35%) sequences obtains 66.4% and 68.4% accuracy for two test sets, respectively. PFRES obtains 6.3-12.4% higher accuracy than the existing methods. The prediction accuracy of PFRES is shown to be statistically significantly better than the accuracy of competing methods. Our method adopts a carefully designed, ensemble-based classifier, and a novel, compact and custom-designed feature representation that includes nearly 90% less features than the representation of the most accurate competing method (36 versus 283). The proposed representation combines evolutionary information by using the PSI-BLAST profile-based composition vector and information extracted from the secondary structure predicted with PSI-PRED. AVAILABILITY: The method is freely available from the authors upon request. 相似文献
46.
Secondary protein structure carries information about local structural arrangements, which include three major conformations: alpha-helices, beta-strands, and coils. Significant majority of successful methods for prediction of the secondary structure is based on multiple sequence alignment. However, multiple alignment fails to provide accurate results when a sequence comes from the twilight zone, that is, it is characterized by low (<30%) homology. To this end, we propose a novel method for prediction of secondary structure content through comprehensive sequence representation, called PSSC-core. The method uses a multiple linear regression model and introduces a comprehensive feature-based sequence representation to predict amount of helices and strands for sequences from the twilight zone. The PSSC-core method was tested and compared with two other state-of-the-art prediction methods on a set of 2187 twilight zone sequences. The results indicate that our method provides better predictions for both helix and strand content. The PSSC-core is shown to provide statistically significantly better results when compared with the competing methods, reducing the prediction error by 5-7% for helix and 7-9% for strand content predictions. The proposed feature-based sequence representation uses a comprehensive set of physicochemical properties that are custom-designed for each of the helix and strand content predictions. It includes composition and composition moment vectors, frequency of tetra-peptides associated with helical and strand conformations, various property-based groups like exchange groups, chemical groups of the side chains and hydrophobic group, auto-correlations based on hydrophobicity, side-chain masses, hydropathy, and conformational patterns for beta-sheets. The PSSC-core method provides an alternative for predicting the secondary structure content that can be used to validate and constrain results of other structure prediction methods. At the same time, it also provides useful insight into design of successful protein sequence representations that can be used in developing new methods related to prediction of different aspects of the secondary protein structure. 相似文献
47.
Crystal structure of a transcription regulator (TM1602) from Thermotoga maritima at 2.3 A resolution
Weekes D Miller MD Krishna SS McMullan D McPhillips TM Acosta C Canaves JM Elsliger MA Floyd R Grzechnik SK Jaroszewski L Klock HE Koesema E Kovarik JS Kreusch A Morse AT Quijano K Spraggon G van den Bedem H Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2007,67(1):247-252
48.
Krishna SS Tautz L Xu Q McMullan D Miller MD Abdubek P Ambing E Astakhova T Axelrod HL Carlton D Chiu HJ Clayton T DiDonato M Duan L Elsliger MA Grzechnik SK Hale J Hampton E Han GW Haugen J Jaroszewski L Jin KK Klock HE Knuth MW Koesema E Morse AT Mustelin T Nigoghossian E Oommachen S Reyes R Rife CL van den Bedem H Weekes D White A Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2007,69(2):415-421
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