The seeming contradiction that K⁺ channels conduct K⁺ ions at maximal throughput rates while not permeating slightly smaller Na⁺ ions has perplexed scientists for decades. Although numerous models have addressed selective permeation in K⁺ channels, the combination of conduction efficiency and ion selectivity has not yet been linked through a unified functional model. Here, we investigate the mechanism of ion selectivity through atomistic simulations totalling more than 400 μs in length, which include over 7,000 permeation events. Together with free-energy calculations, our simulations show that both rapid permeation of K⁺ and ion selectivity are ultimately based on a single principle: the direct knock-on of completely desolvated ions in the channels’ selectivity filter. Herein, the strong interactions between multiple ‘naked’ ions in the four filter binding sites give rise to a natural exclusion of any competing ions. Our results are in excellent agreement with experimental selectivity data, measured ion interaction energies and recent two-dimensional infrared spectra of filter ion configurations.

数十年来，使K ⁺通道以最大通过量传导K ⁺离子而没有渗透到较小的Na ⁺离子的表面上的矛盾使科学家感到困惑。尽管许多模型已经解决了K ⁺通道中的选择性渗透问题，但尚未通过统一的功能模型将传导效率和离子选择性的组合联系在一起。在这里，我们通过总长超过400μs（包括7,000多个渗透事件）的原子模拟研究了离子选择性的机制。结合自由能计算，我们的模拟表明，K ^+的快速渗透离子选择性和离子选择性最终基于一个单一原理：将通道中的完全脱溶剂的离子直接敲除到通道的选择性过滤器中。在此，四个过滤器结合位点中多个“裸”离子之间的强相互作用导致自然排除任何竞争离子。我们的结果与实验选择性数据，测得的离子相互作用能以及最新的过滤器离子构型的二维红外光谱非常吻合。