Dorigo A E, Anderson D G, Busath D D
Department of Chemistry, Colby College, Waterville, Maine 04901, USA.
Biophys J. 1999 Apr;76(4):1897-908. doi: 10.1016/S0006-3495(99)77348-0.
The four Trp dipoles in the gramicidin A (gA) channel modulate channel conductance, and their side chain conformations should therefore be important, but the energies of different conformations are unknown. A conformational search for the right-handed helix based on molecular mechanics in vacuo yielded 46 conformations within 20 kcal/mol of the lowest energy conformation. The two lowest energy conformations correspond to the solid-state and solution-state NMR conformations, suggesting that interactions within the peptide determine the conformation. For representative conformations, the electrostatic potential of the Trp side chains on the channel axis was computed. A novel application of the image-series method of. Biophys. J. 9:1160-1170) was introduced to simulate the polarization of bulk water by the Trp side chains. For the experimentally observed structures, the CHARm toph19 potential energy (PE) of a cation in the channel center is -1.65 kcal/mol without images. With images, the PE is -1.9 kcal/mol, demonstrating that the images further enhance the direct dipole effect. Nonstandard conformations yielded less favorable PEs by 0.4-1.1 kcal/mol.
短杆菌肽A（gA）通道中的四个色氨酸偶极子调节通道电导，因此它们的侧链构象应该很重要，但不同构象的能量尚不清楚。基于真空中分子力学对右手螺旋进行的构象搜索在最低能量构象的20千卡/摩尔范围内产生了46种构象。两个最低能量构象对应于固态和溶液态核磁共振构象，这表明肽内的相互作用决定了构象。对于代表性构象，计算了通道轴上色氨酸侧链的静电势。引入了《生物物理学杂志》9:1160 - 1170中图像序列方法的一种新应用，以模拟色氨酸侧链对大量水的极化作用。对于实验观察到的结构，通道中心阳离子的CHARm toph19势能（PE）在无图像时为 - 1.65千卡/摩尔。有图像时，PE为 - 1.9千卡/摩尔，表明图像进一步增强了直接偶极效应。非标准构象产生的PE不太有利，相差0.4 - 1.1千卡/摩尔。
