Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand-over-hand manner, transiting alternately between one-head-bound (1HB) and two-heads-bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all-atom molecular dynamics simulations we determined the position and orientation of the detached ADP-head relative to the MT-bound head in 1HB state. We showed that in 1HB state when the MT-bound head is in ADP or nucleotide-free state, with its neck linker being undocked, the detached ADP-head and the MT-bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT-bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head-head interaction in 1HB state were identified.

中文翻译：

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全原子分子动力学模拟揭示了驱动蛋白如何从单头结合状态转变为两头结合状态。

驱动蛋白二聚体以递交方式沿着微管（MT）的原丝前进，在单头结合（1HB）和两头结合（2HB）状态之间交替过渡。在1HB状态下，一个由二磷酸腺苷（ADP）结合的头部与MT分离，另一个头部与MT结合。在这里，使用全原子分子动力学模拟，我们确定了分离的ADP头相对于1HB状态下与MT结合的头的位置和方向。我们显示，在1HB状态下，当MT结合的头部处于ADP或无核苷酸状态时，其颈部接头未连接时，分离的ADP头部和MT结合的头部具有高结合能，并且在三磷酸腺苷后（ ATP）结合到MT结合的头部，其颈部接头被对接，大大降低了两个头部之间的结合能。这些结果揭示了驱动蛋白二聚体如何在ATP结合之前保持1HB状态，以及二聚体如何在ATP结合后从1HB转变为2HB状态。确定了在1HB状态下涉及头对头相互作用的关键残基。