Noncontact dipole effects on channel permeation. VI. 5F-and 6F-Trp gramicidin channel currents
Noncontact dipole effects on channel permeation. VI. 5F-and 6F-Trp gramicidin channel currents
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DOI：
10.1016/s0006-3495(02)73959-3
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发表时间：
2002-10-01
影响因子：
3.4
通讯作者：
Busath, DD
中科院分区：
文献类型：
--
作者：
Cole, CD;Frost, AS;Busath, DD
肽侧链的氟化已被证明扰乱短杆菌肽通道电导，而不显着改变平均侧链结构，这是希望，将允许详细分析电流的静电调制。在这里，我们报告了一个1312点钾电流-电压-浓度数据集的homodimeric通道形成grannicidin A（GA）或任何八个氟化色氨酸类似物在卵磷脂和甘油单酯双层。我们拟合的数据与三势垒，两个网站，两个离子（3B 2S）的动力学模型。氟化诱导的速率常数的变化受到相同的因素在两种脂质。速率常数的变化被转换为过渡态的自由能的差异与以前的静电势能差的基础上从头算力场进行比较。该模型允许相当好的拟合（chi（r）（2）= 8.29，自由度为1271）。测量的变化是微妙的。然而，拟合的能量扰动同意与静电预测的8个肽。对于其他三个类似物，拟合的变化表明，减少易位障碍，而不是减少出口障碍预测的静电。
Fluorination of peptide side chains has been shown to perturb gramicidin channel conductance without significantly changing the average side chain structure, which, it is hoped, will allow detailed analysis of electrostatic modulation of current flow. Here we report a 1312-point potassium current-voltage-concentration data set for homodimeric channels formed from grannicidin A (gA) or any of eight fluorinated Trp analogs in both lecithin and monoglyceride bilayers. We fit the data with a three-barrier, two-site, two-ion (3B2S) kinetic model. The fluorination-induced changes in the rate constants were constrained by the same factor in both lipids. The rate constant changes were converted to transition-state free-energy differences for comparison with previous electrostatic potential energy differences based on an ab initio force field. The model allowed a reasonably good fit (chi(r)(2) = 8.29 with 1271 degrees of freedom). The measured changes were subtle. Nevertheless, the fitted energy perturbations agree well with electrostatic predictions for five of the eight peptides. For the other three analogs, the fitted changes suggested a reduced translocation barrier rather than the reduced exit barrier as predicted by electrostatics.