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  • 1
    Electronic Resource
    Electronic Resource
    Characterization of targeting domains by sequence analysis: glycogen-binding domains in protein phosphatases (1998)
    Springer
    Journal of molecular medicine 76 (1998), S. 77-79 
    Details
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050194
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The Genetic Algorithm Applied as a Modelling Tool to Predict the Fold of Small Proteins with Different Topologies (1996)
    Springer
    Journal of molecular modeling 2 (1996), S. 304-306 
    Details
    ISSN: 0948-5023
    Keywords: Genetic algorithm ; Protein structure analysis ; 3D topology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract and Introduction The genetic algorithm exploits the principles of natural evolution. Solution trials are evolved by mutation, recombination and selection until they achieve near optimal solutions [1]. Our own approach has now been developed [2] after a general overview on the application potential for protein structure analysis [3] to a tool to delineate the three-dimensional topology for the mainchain of small proteins [4], no matter whether they are largely helical, are mixed or β-strand rich [5]. Results on several protein examples for these different modelling tasks are presented and compared with the experimentally observed structures (RMSDs are around 4.5-5.5 Å). To start a modelling trial only the protein sequence and knowledge of its secondary structure is required. The fittest folds obtained after the evolution at the end of the simulations yield the three dimensional models of the fold. Current limitations are protein size (generally less than 100 aminoacids), number of secondary structure elements [7-8] and irregular topologies (e.g. ferridoxins). Further, preliminary results from current simulations are illustrated. We now want to apply simple experimental or other information, which is available long before the three-dimensional structure of the protein becomes known, to refine the modelling of the protein fold and tackle also more difficult modelling examples by our tool.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s0089460020304
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  • 3
    Electronic Resource
    Electronic Resource
    Improving Protein Structure Prediction by New Strategies: Experimental Insights and the Genetic Algorithm (1997)
    Springer
    Journal of molecular modeling 3 (1997), S. 312-314 
    Details
    ISSN: 0948-5023
    Keywords: Keywords: Genetic algorithm ; fold prediction ; disulfide bonds ; crowding.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Three different approaches to improve tertiary fold prediction using the genetic algorithm are discussed: (i) Refinement of the search strategy, (ii) combination of prediction and experiment and (iii) inclusion of experimental data as selection criteria into the genetic algorithm. Examples from our current work are presented for refined strategies against crowding in solution space, definition of domain boundaries and secondary structure in combination with experiment, and direct incorporation of experimentally known distance constraints into the fitness function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s008940050043
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  • 4
    Electronic Resource
    Electronic Resource
    Refined Genetic Algorithm Simulations to Model Proteins (1999)
    Springer
    Journal of molecular modeling 5 (1999), S. 317-324 
    Details
    ISSN: 0948-5023
    Keywords: Keywords Genomics, Entropy, Main chain, Structure criteria, Helicobacter pylori
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The advent of completely sequenced genomes is leading to an unprecedented growth of sequence information while adequate structure information is often lacking. Genetic algorithm simulations have been refined and applied as a helpful tool for this question. Modified strategies are tested first on simple lattice protein models. This includes consideration of entropy (protein adjacent water shell) and improved search strategies (pioneer search +14%, systematic recombination +50% in search efficiency). Next, extension to grid free simulations of proteins in full main chain representation is examined. Our protein main chain simulations are further refined by independent criteria such as fitness per residue to judge predicted structures obtained at the end of a simulation. Protein families and protein interactions predicted from the complete H. pylori genomic sequence demonstrate how the full main chain simulations are then applied to model new protein sequences and protein families apparent from genome analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00010719
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  • 5
    Electronic Resource
    Electronic Resource
    Analyzing the Interplay Between Secondary and Tertiary Structure Predictions in Folding Simulations with a Genetic Algorithm (1999)
    Springer
    Journal of molecular modeling 5 (1999), S. 78-89 
    Details
    ISSN: 0948-5023
    Keywords: Keywords Genetic algorithm, Secondary structure prediction, Tertiary structure prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Three different strategies to tackle mispredictions from incorrect secondary structure prediction are analysed using 21 small proteins (22-121 amino acids; 1-6 secondary structure elements) with known three dimensional structures: (1) Testing accuracy of different secondary structure predictions and improving them by combinations, (2) correcting mispredictions exploiting protein folding simulations with a genetic algorithm and (3) applying and combining experimental data to refine predictions both for secondary structure and tertiary fold. We demonstrate that predictions from secondary structure prediction programs can be efficiently combined to reduce prediction errors from missed secondary structure elements. Further, up to two secondary structure elements (helices, strands) missed by secondary structure prediction were corrected by the genetic algorithm simulation. Finally, we show how input from experimental data is exploited to refine the predictions obtained.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s0089490050078
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  • 6
    Electronic Resource
    Electronic Resource
    Isolation and molecular characterization of a surface-bound proteinase of Entamoeba histolytica (1998)
    Oxford BSL : Blackwell Science Ltd
    Molecular microbiology 27 (1998), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Major pathogenic functions of Entamoeba histolytica involved in destruction of host tissues are the degradation of extracellular matrix proteins mediated by secreted cysteine proteinases and contact-dependent killing of host cells via membrane-active factors. A soluble protein with an affinity for membranes was purified from amoebic extracts to apparent homogeneity. N-terminal sequencing and subsequent molecular cloning of the factor revealed that it is a member of the cysteine proteinase family of E. histolytica, which we termed CP5. Further experiments with the purified protein showed that it has potent proteolytic activity that is abrogated in the presence of inhibitors specific for cysteine proteinases. The enzyme firmly associates with membranes retaining its proteolytic activity and it produces cytopathic effects on cultured monolayers. A model of the three-dimensional structure of CP5 revealed the presence of a hydrophobic patch that may account for the potential of the protein to associate with membranes. Immunocytochemical localization of the enzyme to the surface of the amoeba in combination with the recent finding that the gene encoding CP5 is missing in the closely related but non-pathogenic Entamoeba dispar suggests a potential role of the protein in host tissue destruction of E. histolytica.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.1998.00662.x
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  • 7
    Electronic Resource
    Electronic Resource
    Olbers' paradox (1991)
    [s.l.] : Nature Publishing Group
    Nature 351 (1991), S. 21-21 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SIR - At least in a mathematical sense there is yet another solution to Gibers' paradox1: fractals2. Fractal structures like Menger's sponge can have infinite surface area but zero volume and show a self-similar, scaling-independent distribution of their points. Suppose galaxies, clusters and ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/351021b0
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  • 8
    Electronic Resource
    Electronic Resource
    A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks (2000)
    [s.l.] : Nature America Inc.
    Nature biotechnology 18 (2000), S. 326-332 
    Details
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] A set of linear pathways often does not capture the full range of behaviors of a metabolic network. The concept of ‘elementary flux modes’ provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/73786
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  • 9
    Electronic Resource
    Electronic Resource
    Opiates induce long-term increases in prodynorphin-derived peptide levels in the guinea-pig myenteric plexus (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 381-386 
    Details
    ISSN: 1432-1912
    Keywords: Guinea-pig myenteric plexus ; Prodynorphin ; Dynorphin A ; Alpha-neoendorphin ; Feedback ; Opiates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The subcutaneous administration of a single dose of an opiate agonist (levorphanol) or antagonist (naloxone) to guinea pigs results in an at least 3-fold elevation of dynorphin and alpha-neoendorphin-immunoreactivity in the longitudinal muscle myenteric plexus preparation. The effects are time- and dose-dependent, significant elevations first being observed 6 h after treatment and lasting for up to 24 h. Pretreatment levels of opioid peptides were observed after 8 days. Combined injection of the narcotic agonist and antagonist, at sufficiently high doses, resulted in an additive effect of the individual drugs. The respective stereoisomers dextrorphan and (+)-naloxone did not affect prodynorphin-derived peptide concentrations. An increase of endogenous opioids was also observed after administration of the nonopiate clonidine, a compound which, like opiates, alters the activity of the myenteric plexus. It is suggested that feedback mechanisms in the myenteric plexus are responsible for the elevation of endogenous opioid peptides following exposure to exogenous opiates. Using a monoclonal antibody (3-E7), which recognizes virtually all endogenous opioid peptides, it was found that levels of higher molecular material were also increased upon opiate challenge. This suggests that a single dose of an exogenous opiate results in an increase in peptide synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500013
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  • 10
    Electronic Resource
    Electronic Resource
    Mutational analysis of Schizosaccharomyces pombe U4 snRNA by plasmid exchange (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Yeast 8 (1992), S. 647-653 
    Details
    ISSN: 0749-503X
    Keywords: Schizosaccharomyces pombe ; snRNA ; snRNP ; U4 ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: We have developed a system for testing mutations by plasmid exchange in the fission Schizosaccharomyces pombe. This system has been used to test the requirement for different regions of the small nuclear RNA U4 in S. pombe. Surprisingly, five of seven deletion and substitution mutations tested in different regions of U4 prevent the accumulation of the mutant RNA. Substitution of the U4 sequence in stem 1 of the U4/U6 interaction doamain allows accumuation of the mutant U4, but does not supports viability. Two sequences with homology to the Sm binding site are found in the 3′ region of S. pombe U4; substitution of the 3′ sequence of the two does not interfere with accumulation or function of U4, indicating that the 5′ sequence is the functional Sm-binding site.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/yea.320080808
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