Smart O S, Coates G M, Sansom M S, Alder G M, Bashford C L
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Faraday Discuss. 1998(111):185-99; discussion 225-46. doi: 10.1039/a806771f.
The HOLE procedure allows the prediction of the absolute conductance of an ion channel model from its structure. The original prediction method uses an empirically corrected Ohmic method. It is most successful, with predictions being reliable to within a factor of two. A new modification of the procedure is presented in which the self-diffusion coefficients of water molecules from molecular dynamics simulation are used to replace the empirical correction factor. A "prediction" of the conductance for the porin OmpF by the new method is made and shown to be very close to the experimental value. HOLE also allows the prediction of the effect that the addition of non-electrolyte polymers will have on channel conductance. The method has great potential to yield structural information from data provided by single channel recordings but needs further validation by making measurements on channels of known structure. Preliminary results are given of single channel records establishing the effects of non-electrolytes on the conductance of gramicidin D channels. As an example of the potential uses of the procedure application is made to examine the oligomerization of alpha-toxin (alpha-hemolysin) channels. A model for the alpha-toxin hexamer, based on the crystal structure for the heptamer, is generated using molecular mechanics methods. The compatibility of the structures with single channel conductance data is assessed using HOLE.
HOLE程序可根据离子通道模型的结构预测其绝对电导率。最初的预测方法采用经验校正的欧姆方法。该方法最为成功，预测结果的可靠性在两倍以内。本文提出了该程序的一种新改进方法，即使用分子动力学模拟得到的水分子自扩散系数来取代经验校正因子。用新方法对孔蛋白OmpF的电导率进行了“预测”，结果显示与实验值非常接近。HOLE程序还可预测添加非电解质聚合物对通道电导率的影响。该方法很有潜力从单通道记录提供的数据中获取结构信息，但需要通过对已知结构的通道进行测量来进一步验证。给出了关于非电解质对短杆菌肽D通道电导率影响的单通道记录的初步结果。作为该程序潜在用途的一个例子，应用该程序来研究α-毒素（α-溶血素）通道的寡聚化。基于七聚体的晶体结构，使用分子力学方法生成了α-毒素六聚体的模型。利用HOLE程序评估这些结构与单通道电导率数据的兼容性。
