We studied and compared in detail an elusive matrix open (m‐state) and cytoplasmic open (c‐state) state of ADP/ATP carrier (AAC) protein embedded in the DOPC bilayer by microsecond molecular dynamics (MD) simulations. We analyzed both states with and without cardiolipin (CDL) molecules, with a special emphasis on the recently obtained crystallographic structure of the AAC m‐state. The obtained results show that both states of the protein are stable in the DOPC bilayer and impermeable to water. In comparison with the c‐state of AAC, the m‐state is more dynamic, but at the same time possesses a larger occluded area in the protein cavity. Both states of the protein are less flexible in simulations when CDL molecules are present, which is especially visible for the m‐state. Finally, the analysis of the protein conformational changes during MD simulations shows that protein parts at the protein/lipid boundaries are prone to larger conformational changes in contrast to central region of the protein embedded in the bilayer core, thus further supporting the cycling mechanism suggested for ADP/ATP exchange by AAC.

中文翻译：

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线粒体ADP / ATP载体的难以捉摸的基质开放状态的分子动力学模拟

我们通过微秒分子动力学（MD）模拟研究和比较了嵌入在DOPC双层中的ADP / ATP载体（AAC）蛋白的难以捉摸的基质开放（m状态）和胞质开放（c状态）状态。我们分析了有和没有心磷脂（CDL）分子的两种状态，特别强调了最近获得的AAC m状态的晶体结构。获得的结果表明，蛋白质的两种状态在DOPC双层中都是稳定的，并且不透水。与AAC的c状态相比，m状态具有更大的动态性，但同时在蛋白腔中具有较大的封闭区域。当存在CDL分子时，蛋白质的两种状态在模拟中都不太灵活，这对于m状态尤其明显。最后，