Williams Michael R, Tardiff Jil C, Schwartz Steven D
Department of Chemistry and Biochemistry , The University of Arizona , Tucson , Arizona 85721 , United States.
Department of Medicine , The University of Arizona , Tucson , Arizona 85724 , United States.
J Phys Chem Lett. 2018 Jun 21;9(12):3301-3306. doi: 10.1021/acs.jpclett.8b00958. Epub 2018 Jun 5.
The three-state model of tropomyosin (Tm) positioning along filamentous actin allows for Tm to act as a gate for myosin head binding with actin. The blocked state of Tm prevents myosin binding, while the open state allows for strong binding. Intermediate to this transition is the closed state. The details of the transition from the blocked to the closed state and then finally to the open state by Tm have not been fully accessible to experiment. Utilizing steered molecular dynamics, we investigate the work required to move the Tm strand through the extant set of proposed transitions. We find that an azimuthal motion around the actin filament by Tm is most probable in spite of increased initial energy barrier from the topographical landscape of actin.
原肌球蛋白（Tm）沿丝状肌动蛋白定位的三态模型使Tm能够作为肌球蛋白头部与肌动蛋白结合的门控。Tm的阻断状态可防止肌球蛋白结合，而开放状态则允许强结合。此转变的中间状态为关闭状态。Tm从阻断状态转变为关闭状态，最终转变为开放状态的具体细节尚未完全通过实验揭示。利用定向分子动力学，我们研究了将Tm链移动通过现有的一组提议转变所需的功。我们发现，尽管肌动蛋白的地形景观增加了初始能量屏障，但Tm围绕肌动蛋白丝的方位运动是最有可能的。
