Dyneins are an AAA+ motor responsible for motility and force generation toward the minus end of microtubules. Dynein motility is powered by nucleotide-dependent transitions of its linker domain, which transitions between straight (post-powerstroke) and bent (pre-powerstroke) conformations. To understand the dynamics and energetics of the linker, we performed all-atom molecular dynamics simulations of human dynein-2 primed for its power stroke. Simulations revealed that the linker can adopt either a bent conformation or a semi-bent conformation, separated by a 5.7 kT energy barrier. The linker cannot switch back to its straight conformation in the pre-powerstroke state due to a steric clash with the AAA+ ring. Simulations also showed that an isolated linker has a free energy minimum near the semi-bent conformation in the absence of the AAA+ ring, indicating that the linker stores energy as it bends and releases this energy during the powerstroke.

中文翻译：

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动力蛋白启动行程的机制和能量学

动力蛋白是一种 AAA+ 马达，负责向微管负端产生运动和力。动力蛋白的运动性由其接头结构域的核苷酸依赖性转变提供动力，该转变在直（动力冲程后）和弯曲（动力冲程前）构象之间转变。为了了解连接器的动力学和能量学，我们对准备进行动力冲程的人类动力蛋白 2 进行了全原子分子动力学模拟。模拟显示，连接体可以采用弯曲构象或半弯曲构象，并由 5.7 kT 能垒隔开。由于与 AAA+ 环的空间冲突，连接体无法切换回其在预动力冲程状态下的直构象。模拟还表明，在没有 AAA+ 环的情况下，孤立的连接体在半弯曲构象附近具有最小自由能，这表明连接体在弯曲时储存能量，并在动力冲程期间释放该能量。