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      NeuroPred: a tool to predict cleavage sites in neuropeptide precursors and provide the masses of the resulting peptides

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          Abstract

          NeuroPred is a web application designed to predict cleavage sites at basic amino acid locations in neuropeptide precursor sequences. The user can study one amino acid sequence or multiple sequences simultaneously, selecting from several prediction models and optional, user-defined functions. Logistic regression models are trained on experimentally verified or published cleavage data from mollusks, mammals and insects, and amino acid motifs reported to be associated with cleavage. Confidence interval limits of the probabilities of cleavage indicate the precision of the predictions; these predictions are transformed into cleavage or non-cleavage events according to user-defined thresholds. In addition to the precursor sequence, NeuroPred accepts user-specified cleavage information, providing model accuracy statistics based on observed and predicted cleavages. Neuropred also computes the mass of the predicted peptides, including user-selectable post-translational modifications. The resulting mass list aids the discovery and confirmation of new neuropeptides using mass spectrometry techniques. The NeuroPred application, manual, reference manuscripts and training sequences are available at http://neuroproteomics.scs.uiuc.edu/neuropred.html.

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          Most cited references17

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          Comparison of the predicted and observed secondary structure of T4 phage lysozyme.

          Predictions of the secondary structure of T4 phage lysozyme, made by a number of investigators on the basis of the amino acid sequence, are compared with the structure of the protein determined experimentally by X-ray crystallography. Within the amino terminal half of the molecule the locations of helices predicted by a number of methods agree moderately well with the observed structure, however within the carboxyl half of the molecule the overall agreement is poor. For eleven different helix predictions, the coefficients giving the correlation between prediction and observation range from 0.14 to 0.42. The accuracy of the predictions for both beta-sheet regions and for turns are generally lower than for the helices, and in a number of instances the agreement between prediction and observation is no better than would be expected for a random selection of residues. The structural predictions for T4 phage lysozyme are much less successful than was the case for adenylate kinase (Schulz et al. (1974) Nature 250, 140-142). No one method of prediction is clearly superior to all others, and although empirical predictions based on larger numbers of known protein structure tend to be more accurate than those based on a limited sample, the improvement in accuracy is not dramatic, suggesting that the accuracy of current empirical predictive methods will not be substantially increased simply by the inclusion of more data from additional protein structure determinations.
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            Modelling Binary Data

            D. Collett (1991)
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              The crystal structure of the proprotein processing proteinase furin explains its stringent specificity.

              In eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (PCs). Furin, the best-characterized member of the mammalian PC family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax and pathogenic Ebola virus strains. Furin cleaves protein precursors with narrow specificity following basic Arg-Xaa-Lys/Arg-Arg-like motifs. The 2.6 A crystal structure of the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk)-inhibited mouse furin ectodomain, the first PC structure, reveals an eight-stranded jelly-roll P domain associated with the catalytic domain. Contoured surface loops shape the active site by cleft, thus explaining furin's stringent requirement for arginine at P1 and P4, and lysine at P2 sites by highly charge-complementary pockets. The structure also explains furin's preference for basic residues at P3, P5 and P6 sites. This structure will aid in the rational design of antiviral and antibacterial drugs.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Research
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                01 July 2006
                01 July 2006
                14 July 2006
                : 34
                : Web Server issue
                : W267-W272
                Affiliations
                1Department of Animal Sciences, University of Illinois Urbana, IL, USA
                2Department of Chemistry, University of Illinois Urbana, IL, USA
                Author notes
                *To whom correspondence should be addressed. Tel: +1 217 244 7359; Fax: +1 217 244 8068; Email: jsweedle@ 123456uiuc.edu
                Article
                10.1093/nar/gkl161
                1538825
                16845008
                a2676342-d56f-4537-9a8c-a515ac0cff77
                © The Author 2006. Published by Oxford University Press. All rights reserved

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 14 February 2006
                : 20 March 2006
                Categories
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                Genetics
                Genetics

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