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目的：探讨季铵离子在钾通道外部结合位点的结构活性关系．方法：用ＩｎｓｉｇｈｔＩＩ分子建模软件包和ＭＯＰＡＣ６０计算每个季铵离子的水化自由能（ΔＧｈｙｄｒａｔｉｏｎ）、最高占有轨道能量（ＥＨＯＭＯ）和最低未占有轨道能量（ＥＬＵＭＯ）．结合自由能与这些描述参数之间的关系用偏最小二乘法进行回归．结论：一般说来，季铵离子ＥＬＵＭＯ越高，溶剂化就越弱，相应的亲和力就越强．对于比四乙铵大（ＴＥＡ）的季铵离子，其大的分子尺寸不利于它对通道的亲和力．结论：所有季铵离子的通道亲和力与ΔＧｈｙｄｒａｔｉｏｎ和ＥＬＵＭＯ有很好的相关性．
OBJECTIVE: To investigate the structure-activity relationship of quaternary ammonium ions outside the potassium channel binding site. Methods: The hydration free energy (ΔGhydration), highest occupied orbital energy (EHOMO) and lowest unoccupied orbital energy (ELUMO) for each quaternary ammonium ion were calculated using the InsightII Molecular Modeling Software Package and MOPAC 6.0. The relation between free energy and these descriptors is regressed by partial least squares. Conclusion: In general, the higher ELUMO of the quaternary ammonium ion, the weaker the solvation and the higher the corresponding affinity. For quaternary ammonium ions larger than tetraethylammonium (TEA), its large molecular size is detrimental to its affinity for the channel. Conclusion: The channel affinity of all quaternary ammonium ions correlates well with ΔGhydration and ELUMO.