Many membrane channels, transporters, and receptors utilize a pH gradient or proton coupling to drive functionally relevant conformational transitions. Conventional molecular dynamics simulations employ fixed protonation states, thus neglecting the coupling between protonation and conformational equilibria. Here we describe the membrane-enabled hybrid-solvent continuous constant pH molecular dynamics method for capturing atomic details of proton-coupled conformational dynamics of transmembrane proteins. Example protocols from our recent application studies of proton channels and ion/substrate transporters are discussed.

中文翻译：

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跨膜蛋白的连续恒定pH分子动力学

许多膜通道，转运蛋白和受体利用pH梯度或质子偶联来驱动功能相关的构象转变。常规分子动力学模拟采用固定的质子化状态，因此忽略了质子化和构象平衡之间的耦合。在这里，我们描述了膜功能的混合溶剂连续恒定pH分子动力学方法，用于捕获跨膜蛋白的质子偶联构象动力学的原子细节。讨论了我们最近对质子通道和离子/底物转运蛋白的应用研究中的示例方案。