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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 31 (1992), S. 7948-7956 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 19-33 
    ISSN: 0887-3585
    Keywords: Discover program ; protein dynamics ; computer simulation ; protein motions ; counterions ; dielectric ; protein electrostatics ; aqueous simulation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In this report we examine several solvent models for use in molecular dynamics simulations of protein molecules with the Discover program from Biosym Technologies. Our goal was to find a solvent system which strikes a reasonable balance among theoretical rigor, computational efficiency, and experimental reality. We chose phage T4 lysozyme as our model protein and analyzed 14 simulations using different solvent models. We tested both implicit and explicit solvent models using either a linear distance-dependent dielectric or a constant dielectric. Use of a linear distance-dependent dielectric with implicit solvent significantly diminished atomic fluctuations in the protein and kept the protein close to the starting crystal structure. In systems using a constant dielectric and explicit solvent, atomic fluctuations were much greater and the protein was able to sample a larger portion of conformational space. A series of nonbonded cutoff distances (9.0, 11.5, 15.0, 20.0 Å) using both abrupt and smooth truncation of the nonbonded cutoff distances were tested. The method of dual cutoffs was also tested. We found that a minimum nonbonded cutoff distance of 15.0 Å was needed in order to properly couple solvent and solute. Distances shorter than 15.0 Å resulted in a significant temperature gradient between the solvent and solute. In all trajectories using the proprietary Discover switching function, we found significant denaturation in the protein backbone; we were able to run successful trajectories only in those simulations that used no switching function. We were able to significantly reduce the computational burden by using dual cutoffs and still calculate a quality trajectory. In this method, we found that an outer cutoff distance of 15.0 Å and an inner cutoff distance of 11.5 worked well. While a 10 Å shell of explicit water yielded the best results, a 6 A shell of water yielded satisfactory results with nearly a 40% reduction in computational cost. © 1994 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 382-399 
    ISSN: 0887-3585
    Keywords: protein secondary structure ; amino acid sequence ; distributions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The conditional probability, P(σ|x), is a statement of the probability that the value of σ will be found given the prior information that a value of x has been observed. Here σ represents any one of the secondary structure types, α, β, τ, and ρ for helix, sheet, turn, and random, respectively, and x represents a sequence attribute, including, but not limited to: (1) hydropathy; (2) hydrophobic moments assuming helix and sheet; (3) Richardson and Richardson helical N-cap and C-cap values; (4) Chou-Fasman conformational parameters for helix, Pα, for sheet, Pβ, and for turn, Pτ; and (5) Garnier, Osguthorpe, and Robson (GOR) information values for helix, Iα, for sheet, Iβ, for turn, I,τ, and for random structure, Iρ.Plots of P (σ|x) vs. x are demonstrated to provide information about the correlation between structure and attribute, σ and x. The separations between different P (σ|x) vs. x curves indicate the capacity of a given attribute to discriminate between different secondary structural types and permit comparison of different attributes. P (α|x), P (β|x), P (τ|x) and P (ρ|x) vs. x plots show that the most useful attributes for discriminating helix are, in order: hydrophobic moment assuming helix 〉 Pα » N-cap 〉 C-cap ≈ Iα ≈ Iτ. The information value for turns, Iτ, was found to discriminate helix better than turns. Discrimination for sheet was found to be in the following order: Iβ » Pβ ≈ hydropathy 〉 Iρ ≈ hydrophobic moment assuming sheet.Three attributes, at their low values, were found to give significant discrimination for the absence of helix: Iα ≈ Pα ≈ hydrophobic moment assuming helix. Also, three other attributes were found to indicate the absence of sheet: Pβ » Iτ ≈ hydropathy. Indications of the absence of σ could be as useful for some applications as the indication of the presence of σ.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 41 (1997), S. 533-544 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A dynamical model of interdomain “hinge bending” of T4 lysozyme in aqueous solution has been developed on the basis of molecular dynamics (MD) simulation. The MD model study provides a description of the conformational reorganization expected to occur for the protein in aqueous solution as compared to the crystalline environment. Three different 500 ps molecular dynamics simulations were calculated, each using a distinctly different crystal conformation of T4 lysozyme as the starting points of the MD simulations. Crystal structures of wild-type lysozyme and “open” and “closed” forms of M6I variant structures were analyzed in this study. Large-scale, molecular-conformational rearrangements were observed in all three simulations, and the largest structural change was found for the open form of the M6I allomorph. All three simulated proteins had closed relative to the wild-type crystal structure, and the closure of the “jaws” of the active site cleft occurred gradually over the time course of the trajectories. The time average MD structures, calculated over the final 50 ps of each trajectory, had all adapted to conformations more similar to each other than to their incipient crystal forms. Using a similar MD protocol on cytochrome P450BM-3 [M. D. Paulsen and R. L. Ornstein (1995) Proteins: Structure Function and Genetics, Vol. 27, pp. 237-243] we have found that the opposite type of motion relative to the starting crystal structure, that is, the open form of the crystal structure, had opened to a greater degree relative to the incipient crystal structure form. Therefore we do not believe that either result is merely a simulation artifact, but rather the protein dynamics are due to protein relaxation in the absence of crystal packing forces in the simulated solution environments. © 1997 John Wiley & Sons, Inc. Biopoly 41: 533-544, 1997
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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