Department of Computational Science and Engineering, Nagoya University, Nagoya 464-8603, Japan.
Phys Chem Chem Phys. 2014 Apr 14;16(14):6441-7. doi: 10.1039/c3cp54464h. Epub 2014 Feb 11.
A long-standing controversy on the mechanism of an actomyosin motor is the role of the Brownian motion of the myosin head in force generation. In order to shed light on this problem, we calculate free-energy landscapes of interaction between an actin filament and the head (S1) of myosin II by using a coarse-grained model of actomyosin. The results show that the free-energy landscape has a global gradient toward the strong-binding site on actin filament, which explains the biased Brownian motion of myosin S1 observed in a single-molecule experiment [Kitamura et al., Nature, 1999, 397, 129 and Biophysics, 2005, 1, 1]. The distinct global gradient in the landscape is brought about only when the conformation of loop 2 at the actin interface of myosin S1 is flexible. The conformational flexibility of loop 3 also contributes to the gradient in the landscape by compensating the role of loop 2. Though the structure of loop 2 is expanded in the weak-binding state, loop 2 shows the larger fluctuation of compaction and expansion due to the actin-myosin interactions as myosin S1 moves toward the strong-binding site on actin filament. Hence, the increase in the compaction-expansion fluctuation of loop 2, the stronger binding of myosin to actin, and the biased Brownian motion of myosin S1 are coupled with each other and should take place in a concurrent way. This predicted coupling should provide opportunities to further test the hypothesis of the biased Brownian motion in actomyosin.
肌球蛋白头部的布朗运动在力的产生中的作用一直是肌球蛋白马达机制的一个长期争议点。为了解决这个问题，我们使用肌球蛋白和肌动蛋白的粗粒模型来计算肌球蛋白头部（S1）与肌动蛋白丝之间的相互作用的自由能景观。结果表明，自由能景观具有朝向肌动蛋白丝强结合位点的全局梯度，这解释了在单分子实验中观察到的肌球蛋白 S1 的偏向布朗运动[Kitamura 等人，《自然》，1999，397，129 和《生物物理学》，2005，1，1]。只有当肌球蛋白 S1 与肌动蛋白界面上的环 2 构象具有柔韧性时，景观中的这种独特的全局梯度才会出现。环 3 的构象灵活性通过补偿环 2 的作用也有助于景观中的梯度。尽管环 2 的结构在弱结合状态下扩展，但由于肌球蛋白 S1 向肌动蛋白丝的强结合位点移动，环 2 表现出更大的压缩和扩展波动。因此，环 2 的压缩-扩展波动增加、肌球蛋白与肌动蛋白的结合增强以及肌球蛋白 S1 的偏向布朗运动相互关联，应该以并行的方式发生。这种预测的耦合应该为进一步测试肌球蛋白和肌动蛋白中的偏向布朗运动假说提供机会。
