Simulating the dynamics of the mechanochemical cycle of myosin-V
Simulating the dynamics of the mechanochemical cycle of myosin-V
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DOI：
10.1073/pnas.1700318114
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发表时间：
2017-02-28
影响因子：
11.1
通讯作者：
Warshel, Arieh
中科院分区：
文献类型：
--
作者：
Mukherjee, Shayantani;Alhadeff, Raphael;Warshel, Arieh
肌球蛋白-V的循环的详细动力学探索模拟方法，检查能量驱动的运动的性质。我们的研究开始于朗之万动力学（LD）模拟一个非常粗糙的景观与一个单一的限速障碍，并再现失速力量和手的手在手的动态。然后，我们考虑了一个更现实的景观，并使用时间依赖的蒙特卡罗（MC）模拟，允许轨迹足够长，以再现力/速度特性的S形相关，同时也再现手的手的运动。总的来说，我们的研究表明，下坡向上到向下的过程（通常称为动力冲程机制）的概念是完整肌球蛋白V循环的能量学的结果，本身不是定向运动或力产生的来源。目前的工作进一步强调，需要使用定义良好的能源景观在一般的研究分子马达，特别是肌球蛋白。
The detailed dynamics of the cycle of myosin-V are explored by simulation approaches, examining the nature of the energy-driven motion. Our study started with Langevin dynamics (LD) simulations on a very coarse landscape with a single rate-limiting barrier and reproduced the stall force and the hand-over-hand dynamics. We then considered a more realistic landscape and used timedependent Monte Carlo (MC) simulations that allowed trajectories long enough to reproduce the force/velocity characteristic sigmoidal correlation, while also reproducing the hand-over-hand motion. Overall, our study indicated that the notion of a downhill lever-up to lever-down process (popularly known as the powerstroke mechanism) is the result of the energetics of the complete myosin-V cycle and is not the source of directional motion or force generation on its own. The present work further emphasizes the need to use well-defined energy landscapes in studying molecular motors in general and myosin in particular.