computer modeling in molecular biology.pdf

160 Benoit Rouxremain in close contact with the Na' ion during both the reactive and non-reactivetrajectories and it is clear that the permeation process does not proceed by a vacancydiffusion mechanism as is often suggested [21, 891.Table 6-2. Transition rate of Na+ .PropertiesActivation energy A W *18.9 kJ/molWell frequency vwell4.0 ps-'Eyring's Transition State Theory rate kTsT2.1 x 109 s-lTransmission coefficient K 0.11Transition rate k = ~k~~2.3 x lo's-'6.3.4.3 Comparison with ExperimentsComparison of the calculated channel conductance with experimental values shouldbe made with caution since many of the features of the full gramicidin channel arenot included in the periodic P-helix system. At best the periodic P-helix model is avalid description for the interior of the pore and end effects have been neglected. Theexpression used for A,,, is based on the assumption that the maximum conductanceunder a saturating concentration is determined only by the translocation rateof Na+ inside a singly-occupied channel (see Section 6.2). Experimental observationsindicate that permeation of Na' through the gramicidin channel does notobey perfectly this simple model. Deviations of Na' fluxes from the one-ion poresaturation have been attributed to double-occupancy of the gramicidin channel [27].Furthermore, it is possible that the maximum conductance, A,,,, is affected by factorsothers than the translocation through the channel. For instance, it has beenobserved that the maximum conductane of Na' depends on the composition of thelipid membrane; the maximum conductance of Na' ion through the gramicidin Achannel measured in phosphatidylethanolamine (PE) membranes is 14.6 ps [24, 261,about a factor of two smaller than the value of 27 ps measured in glycerylmonooleate(GMO) [21]. Nevertheless, in spite of these uncertainties, the calculated valueof 7 pmho has the correct order of magnitude, showing that the local interactionsin the P-helix per se during the translocation of Na' give rise to significant activationbarriers that could account for the observed diffusion rate.