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  • Articles: DFG German National Licenses  (5)
  • 1995-1999  (5)
  • 1910-1914
  • Biochemistry and Biotechnology  (5)
  • 1
    ISSN: 0887-3585
    Keywords: de novo design ; protein structure ; inverse folding ; genetic algorithms ; 1H NMR ; CD ; peptide ; protein folding ; methanol ; ethylene glycol ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In response to the Paracelsus Challenge (Rose and Creamer, Proteins, 19:1-3, 1994), we present here the design, synthesis, and characterization of a helical protein, whose sequence is 50% identical to that of an all-β protein. The new sequence was derived by applying an inverse protein folding approach, in which the sequence was optimized to “fit” the new helical structure, but constrained to retain 50% of the original amino acid residues. The program utilizes a genetic algorithm to optimize the sequence, together with empirical potentials of mean force to evaluate the sequence-structure compatibility. Although the designed sequence has little ordered (secondary) structure in water, circular dichroism and nuclear magnetic resonance data show clear evidence for significant helical content in water/ethylene glycol and in water/methanol mixtures at low temperatures, as well as melting behavior indicative of cooperative folding. We believe that this represents a significant step toward meeting the Paracelsus Challenge.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0887-3585
    Keywords: antiparallel β-sheet ; twist ; protein folding ; side chain interactions ; branched amino acids ; cystine-rich proteins ; side chain packing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cross-strand pair correlations are calculated for residue pairs in antiparallel β-sheet for two cases: pairs whose backbone atoms are hydrogen bonded together (H-bonded site) and pairs which are not (non-H-bonded site). The statistics show that this distinction is important. When glycine is located on the edge of a sheet, it shows a 3:1 preference for the H-bonded site. Thestrongest observed correlations are for pairs of disulfide-bonded cystines, many of which adopt a close-packed conformation with each cystine in a spiral conformation of opposite chirality to its partner. It is likely that these pairs are a signature for the family of small, cystine-rich proteins. Most other strong positive and negative correlations involve charged and polar residues. It appears that electrostatic compatibility is the strongest factor affecting pair correlation. Significant correlations are observed for β- and γ-branched residues inthe non-H-bonded site. An examination of the structures showsa directionality in side chain packing. There is a correlation between (1) the directionality in the packing interactions of non-H-bonded β- and γ-branched residue pairs, (2) the handedness of the observed enantiomers of chiral β-branched side chains, and (3) the handedness of the twist of β-sheet. These findings have implications for the formation of β-sheets during protein folding and the mechanism by which the sheet becomes twisted. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Chicester [u.a.] : Wiley-Blackwell
    Journal of Molecular Recognition 10 (1997), S. 73-87 
    ISSN: 0952-3499
    Keywords: glycopeptide antibiotics ; free energy perturbation ; molecular dynamics simulation ; molecular recognition ; computer-assisted drug design ; 2D NMR ; simulated annealing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The antimicrobial activity of vancomycin and related glycopeptide antibiotics is due to stereospecific recognition of polypeptide components in bacterial cell walls. To better understand how these antibiotics recognize polypeptide determinants, we have developed dynamic models of the complexes formed by the vancomycin aglycon and two different dipeptide ligands, Ac-D-ala-D-ala and Ac-D-ala-gly. Molecular dynamics simulations of the two complexes, initially conditioned with distance constraints derived from two-dimensional nuclear magnetic resonance (NMR) studies, are conformationally stable and propagate in a manner consistent with the NMR-derived constraints after the constraints are removed. Free energy calculations accurately predict the relative binding affinity of these two complexes and help validate the simulation models for detailed structural analysis. Although the two ligands adopt similar conformations when bound to the antibiotic, there are clear differences in the configuration of intermolecular hydrogen bonds, the overall shape of the antibiotic, and other structural features of the two complexes. This analysis illustrates how complex structural and dynamic factors interrelate and contribute to differences in binding affinity. © 1997 John Wiley & Sons, Ltd.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 125-135 
    ISSN: 0006-3592
    Keywords: ultrafiltration ; proteins ; colloidal interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A rigorous dynamic mathematical model for predicting the rate of ultrafiltration of proteins has been developed. The model is based on sophisticated descriptions of the protein-protein interactions within the layer close to the membrane surface which are responsible for controlling permeation rate. Electrostatic interactions are accounted for by a Wigner-Seitz cell approach, including a numerical solution of the nonlinear Poisson-Boltzmann equation. London-van der Waals forces are calculated using a computationally efficient means of approximating screened, retarded Lifshitz-Hamaker constants. Configurational entropy effects are calculated using an equation of state giving excellent agreement with molecular dynamic data. Electroviscous effects are also taken into account. These descriptions of protein-protein interactions are used to develop an a priori model, with no adjustable parameters, that allows quantitative prediction of the rate of filtration of proteins as a function of zeta potential (and hence pH), ionic strength, applied pressure, protein size, and membrane resistance. A comparison with experimental data for the filtration of bovine serum albumin (BSA) shows that the model is in excellent agreement with such data. © 1996 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Chemical Technology AND Biotechnology 64 (1995), S. 317-324 
    ISSN: 0268-2575
    Keywords: array ; combinatorial ; diversity ; library ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: A Comprehensive review of the tractic and strategies that are available to the drug discovery process using combinatorial techniques.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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