Gramicidin channels

Nevertheless, the technique suffers from a severe time scale problem -the trajectories are computed for (at most) a few nanoseconds. This is far too short compared to times required for many processes in biophysics. For example, the ii to T conformational transition in hemoglobin lasts tens of microseconds [1], and the typical time for ion migration through the gramicidin channel is hundreds of nanoseconds. This limits (of course) our ability to make a meaningful comparison to experiments, using MD. 

Wallace, B. A., 1990. Gramicidin channels and pores. Annual Review of Biophysics and Biophysical Chemistry 19 127—157. 

II The Channel Mechanism of Ion Transport The Gramicidin Channel Model 181... 

D Free Energy Profile for Cation Passage Through the Gramicidin Channel 188... 

Fig. 8. A. Free energy profile for Na+ movement through the malonyl Gramicidin channel. Calculated using Eyring rate theory and the locations of binding sites in the channel.

Fig. 10. Calculated sodium ion single channel currents for the malonyl Gramicidin channel and comparison with experimental data points using four different models all of which fit the data well but only one of which, B., is correct. The point to be made is that both the independent determination of rate constants and of the binding site locations are required.

B. In vacuo calculation of a librated state of the Gramicidin channel showing the peptide NH moieties to be librated into the channel. This is a relatively high energy conformation, some 8 kcal/mole higher than in A. C. M. Venkatachalam and D. W. Urry, unpublished results... 

Li+ (0.77) < Na+ (1.0) < K+ (1.48) < Rb+ (1.55) < Cs+ (1.56). While indeed the order is the same, the significant point is that the range of discrimination has been expanded by almost an order of magnitude. The concern then becomes the mechanism whereby the Gramicidin channel effects this enhancement of selectivity. An important source of selectivity that must be considered is the relative solvation energy of water... 

Typically, the insertion induces sharp variation of the membrane profile at the distances 0.5-1.0nm from the membrane-peptide interface [79-82]. The steepness of this perturbation indicates that the short-A, behavior of membrane moduli must be important in the estimates of the elastic energy. In addition, a peptide inserted in a membrane almost certainly perturbs the membrane s elastic moduli in the immediate vicinity of the inclusion. Both these effects, membrane nonlocality and nonuniform modification of elastic properties by insertions, might play an important role in resolving the contradiction between the local calculations [80] and the experimental data for the mean lifetime of a gramicidin channel [81,109,110]. ... 

O Connell, A. M. Koeppe, R. E., II Andersen, O. S., Kinetics of gramicidin channel formation in lipid bilayers Transmembrane monomer association, Science 250, 1256-1259 (1990). 

Fig. 6.14 A gramicidin channel consisting of two helical molecules in the head-to-head position. (According to V. I. 

Four helical models have been proposed for the conformation of the gramicidin channel in order to accommodate these and other data (see Fig. 23) ... 

The bonding of K+ and Na+ to A-methylacetamide is of interest64 in studies of the interaction of these ions with peptides and proteins, and particularly studies of the ion transport through transmembrane channels such as the gramicidin channel. Roux and Karplus35 have used the complexation of the given alkali ion with two N-methylacetamide molecules and two water molecules as a model for interactions occurring in transmembrane channels. 

Roux, B. 1993. Non-additivity in Cation-peptide Interactions. A Molecular Dynamics and Ab Initio Study of Na+ in the Gramicidin Channel. Chem. Phys. Letters 212,231-240. 

Pomes, R. Roux, B., Molecular mechanism of H+ conduction in the single-file water chain of the gramicidin channel, Biophys. J. 2002, 82, 2304-2316... 

Allen, T.W. Andersen, O.S. Roux, B., Energetics of ion conduction through the gramicidin channel, Proc. Natl Acad. Sci. USA 2004,101, 117-122. 

Conduction along water wires may as well be the dominant mechanism in the permeation of protons in channels an MD study of proton transport through a gramicidin channel can be found in, for example, [156]. 

Left and center Two gramicidin A molecules associate to span a cell membrane. Right Axial view showing ion channel. [Structure from B. Roux, "Computational Studies of the Gramicidin Channel." Acc. Chem. Res. 2002,35,366. based on solid-state nuclear magnetic resonance. Schematic at left from L. Stryer. Biochemistry,... 

Figure 4 Schematic representation of gramicidin channels in membranes...

Hladky, S. Haydon, D.A. (1984). Ion movements in gramicidin channels. Curr. Topics in Membranes and Transport 21,327-372. 

Cross, T. A., Arseniev, A., Cornell, B. A., etal, Gramicidin channel controversy - revisited. Nature Structural Biology 1999,6,610-611. 

Benoit Roux s group is using molecular dynamics (MD) simulations to elucidate the fundamental principles governing the transport of ions with a special interest in constructing detailed atomic models of the gramicidin channel.29 They also use MD simulations and free energy methodologies to study... 

B. Roux and M. Karplus, Annu. Rev. Biomol. Struct. Dyn., 23, 731 (1994). Molecular Dynamics Simulations of the Gramicidin Channel. 

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