Research School of Biology, Australian National University, Canberra, Australia.
Biophys J. 2011 Dec 7;101(11):2652-60. doi: 10.1016/j.bpj.2011.10.029.
The conduction properties of the voltage-gated potassium channel Kv1.3 and its modes of interaction with several polypeptide venoms are examined using Brownian dynamics simulations and molecular dynamics calculations. Employing an open-state homology model of Kv1.3, we first determine current-voltage and current-concentration curves and ascertain that simulated results accord with experimental measurements. We then investigate, using a molecular docking method and molecular dynamics simulations, the complexes formed between the Kv1.3 channel and several Kv-specific polypeptide toxins that are known to interfere with the conducting mechanisms of several classes of voltage-gated K(+) channels. The depths of potential of mean force encountered by charybdotoxin, α-KTx3.7 (also known as OSK1) and ShK are, respectively, -19, -27, and -25 kT. The dissociation constants calculated from the profiles of potential of mean force correspond closely to the experimentally determined values. We pinpoint the residues in the toxins and the channel that are critical for the formation of the stable venom-channel complexes.
利用布朗动力学模拟和分子动力学计算研究了电压门控钾通道 Kv1.3 的传导特性及其与几种多肽毒液的相互作用模式。采用 Kv1.3 的开放态同源模型，我们首先确定了电流-电压和电流-浓度曲线，并确定模拟结果与实验测量相符。然后，我们使用分子对接方法和分子动力学模拟研究了 Kv1.3 通道与几种已知干扰几类电压门控 K(+)通道传导机制的 Kv 特异性多肽毒素形成的复合物。Charybdotoxin、α-KTx3.7（也称为 OSK1）和 ShK 遇到的平均力势的深度分别为-19、-27 和-25 kT。从平均力势曲线计算得到的离解常数与实验测定值非常吻合。我们确定了毒素和通道中对于形成稳定的毒-通道复合物至关重要的残基。
