细胞内的货物运输对健康细胞至关重要，这需要基于微管的电机，包括kinesin.微管的α和β微管蛋白的C末端尾巴（E钩）已被证明在驱动蛋白和微管蛋白之间的相互作用中起重要作用。这里,我们在E-hook相关分析中实现了多尺度计算方法，包括电子钩的灵活性研究，在驱动蛋白和微管蛋白之间的结合界面处的结合力计算，驱动蛋白和微管蛋白表面的静电势计算。我们的结果表明，E-hook在结合过程中具有多种功能：E-hook利用自己的高柔性来增加达到驱动蛋白的机会；E-hook帮助微管蛋白对驱动蛋白更具吸引力。此外,我们还观察到α和β微管蛋白之间的差异：β微管蛋白显示出比α微管蛋白更高的灵活性；β微管蛋白在不同距离对驱动蛋白产生更强的吸引力（大约是强度的两倍），无论结构中是否有E形钩。这些事实可能表明，与α微管蛋白相比，β微管蛋白更有助于吸引和捕获驱动蛋白到微管。总的来说,这项工作为微管研究提供了启示，这也将有利于神经退行性疾病的治疗，癌症治疗,和未来的预防措施。
Cargo transport within cells is essential to healthy cells, which requires microtubules-based motors, including kinesin. The C-terminal tails (E-hooks) of alpha and beta tubulins of microtubules have been proven to play important roles in interactions between the kinesins and tubulins. Here, we implemented multi-scale computational methods in E-hook-related analyses, including flexibility investigations of E-hooks, binding force calculations at binding interfaces between kinesin and tubulins, electrostatic potential calculations on the surface of kinesin and tubulins. Our results show that E-hooks have several functions during the binding process: E-hooks utilize their own high flexibilities to increase the chances of reaching a kinesin; E-hooks help tubulins to be more attractive to kinesin. Besides, we also observed the differences between alpha and beta tubulins: beta tubulin shows a higher flexibility than alpha tubulin; beta tubulin generates stronger attractive forces (about twice the strengths) to kinesin at different distances, no matter with E-hooks in the structure or not. Those facts may indicate that compared to alpha tubulin, beta tubulin contributes more to attracting and catching a kinesin to microtubule. Overall, this work sheds the light on microtubule studies, which will also benefit the treatments of neurodegenerative diseases, cancer treatments, and preventions in the future.
