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  • Computational Chemistry and Molecular Modeling  (4)
  • dynamic channel  (1)
  • electrophysiology without electrodes  (1)
  • 1
    ISSN: 1432-1424
    Keywords: gramicidin channel ; temperature dependence ; single channel current histograms ; peptide libration mechanism ; nonlinear Arrhenius plots ; metastable states ; dynamic channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary A study of the temperature dependence of gramicidin A conductance of K+ in diphytanoyllecithin/n-decane membranes shows the plot of In (single channel conductance) as a function of reciprocal temperature to be nonlinear for the most probable set of conductance, states. These results are considered in terms of a series of barriers, of the dynamics of channel conformation,vis-a-vis the peptide libration mechanism, and of the effect of lipid viscosity on side chain motions again as affecting the energetics of peptide libration.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 89 (1986), S. 107-111 
    ISSN: 1432-1424
    Keywords: quadrupolar nuclear magnetic resonance ; rotational correlation times and off-rate constants ; potassium-39 NMR ; gramicidin channel transport ; ion transport specificity ; electrophysiology without electrodes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary A potassium-39 NMR study of potassium ion interaction with the gramicidin transmembrane channel in phospholipid bilayers at high ion activity is reported which allows determination of a weak binding constant, K b w ≃8.3/m, and an off-rate constant for the weak site,k off w ≃2.6×107/sec. These values are interpreted with the aid of additional NMR data as the binding constant for formation of the doubly occupied channel state and the rate constant for an ion leaving the doubly occupied state. Considering the singly occupied channel state for the potassium ion to be “electrically silent” at 1 molar ion activity, as with the sodium ion, the single-channel conductance for 100 mV and 30°C calculated to be 29 pS, and using the same approximation with previous NMR results on the sodium and rubidium ions, reasonable conductance ratios were calculated. Further experimental estimates of the other three constants with the experimental location of binding sites and Eyring rate theory to introduce voltage dependence allowed a more complete calculation of the two-site channel. The single-channel conductance for potassium ion is calculated to be 24 pS at 1m activity and 26 pS at 0.6m activity, which compares for diphytanoyl phosphatidylcholine membranes to an experimental most probable single-channel conductance of 25 pS and a mean channel conductance of 20 pS. The calculated conductance ratios using NMR-derived constants were γ(K)/γ(Na)=2.0 and γ(Rb)/γ(Na)=4.3. These results are close to the experimental values and provide further basis for the use of NMR of quadrupolar ions to provide information on the ionic mechanism of channel transport.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Single-channel studies have shown that there exist a multiplicity of conducting states in Gramicidin A (GA). In an earlier work presented at this symposium, it was proposed that such a multiplicity may be expected from different long-lived side-chain distributions available for the channel molecule. In order to test this hypothesis, Leu5-Gramicidin A was synthesized and the effect of replacing the L · Ala5 residue by L · Leu5 was analyzed. First, molecular mechanics calculations on Leu5-Gramicidin A are presented. Then the single-channel conductance sweeps obtained for Leu5-GA are automatically analyzed in the computer using specifically developed algorithms. The results show a dramatic decrease in the multiplicity of states due to the Leu5 substitution. This experimental result is discussed in the light of structural concepts emerging from molecular mechanics calculations.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 20 (1981), S. 385-399 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The significance of the gramicidin channel, its structural elements, and the importance of the peptide libration mechanism are reviewed. Elemental ionic processes of the single-channel currents are considered, which indicate the possibility of two- and three-site models. Data are presented which demonstrate the absence of interactions required for the three-site model, and the resulting free-energy profile for the two-site model is given for the most probable conducting state. The need to extend analyses to include an understanding of multiple conformational states is outlined, and results from approximate conformational energy calculations are presented showing that there are numerous low-energy conformations for the side chains of gramicidin. Specifically the interactions between L·Trp9 and L·Trp15 side chains and between D·Leu4…D·Leu10 are analyzed to show the existence of several energy minima separated by appreciable barriers. These findings provide the basis for understanding facilitated entry of the second ion into the channel and the occurrence of lipid-dependent dispersion of conductance states. Finally perspectives of the molecular mechanism of anesthetics are discussed relevant to the gramicidin channel mean lifetime and single-channel currents.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 5 (1984), S. 64-71 
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: The degrees of conformational freedom of poly L-D β-helical chain are analyzed consistent with the helical parameters of gramicidin A structure. From conformational energy calculations, “helical librations” that can be sustained by this structure are described and the energy of libration as a function of the cavity size is presented. Two different modes of conformational change are identified corresponding to librations of all L-D-peptide units or all D-L-peptide units while retaining the helical parameters. Such helical librations are considered relative to conformational perturbations due to the presence of an ion in the channel.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 4 (1983), S. 461-469 
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: Conformational energy calculations are presented for the head-to-head dimerized β helices for Gramicidin A transmembrane channel structures. The calculations take into account both left- and right-handed β helices, and various side-chain conformations. The energetics of the dimerization is studied by considering various docking geometries. It is concluded from these vacuum-energy calculations that the lowest energy conformation for the channel dimer is that comprised of left-handed β helices.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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