Mechanical properties of a complete microtubule revealed through molecular dynamics simulation.
Mechanical properties of a complete microtubule revealed through molecular dynamics simulation.
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DOI：
10.1016/j.bpj.2010.04.038
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发表时间：
2010-07
影响因子：
3.4
通讯作者：
D. Wells;A. Aksimentiev
中科院分区：
文献类型：
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作者：
D. Wells;A. Aksimentiev
微管（MTs）是最大类型的细胞丝，在从有丝分裂和减数分裂到鞭毛运动的过程中必不可少。许多过程严重依赖于MT的机械性能，但弹性模量，特别是杨氏模量，并没有直接在实验中显示，而是测量弯曲刚度或对径向变形的响应。分子动力学（Molecular dynamics， MD）是一种通过计算来研究单个生物分子力学性质的方法。通常，MD需要分子的原子分辨率结构，这对于包括MT在内的许多系统来说是不可用的。通过结合低温电子显微镜和电子晶体学的结构信息，我们构建了一个完整MT的全原子模型，并使用MD来确定其力学性能。模拟结果显示了非线性轴向应力-应变行为，在拉伸下表现出明显的软化，在径向压缩下可能出现塑性变形转变，并且在两种感觉的扭转下表现出明显的不对称性。这项工作证明了结合不同层次的结构信息来产生适合定量MD模拟的全原子模型的可能性，这扩展了适用于MD方法的系统范围，并将使我们的微观生物学知识取得令人兴奋的进展。
Microtubules (MTs) are the largest type of cellular filament, essential in processes ranging from mitosis and meiosis to flagellar motility. Many of the processes depend critically on the mechanical properties of the MT, but the elastic moduli, notably the Young's modulus, are not directly revealed in experiment, which instead measures either flexural rigidity or response to radial deformation. Molecular dynamics (MD) is a method that allows the mechanical properties of single biomolecules to be investigated through computation. Typically, MD requires an atomic resolution structure of the molecule, which is unavailable for many systems, including MTs. By combining structural information from cryo-electron microscopy and electron crystallography, we have constructed an all-atom model of a complete MT and used MD to determine its mechanical properties. The simulations revealed nonlinear axial stress-strain behavior featuring a pronounced softening under extension, a possible plastic deformation transition under radial compression, and a distinct asymmetry in response to the two senses of twist. This work demonstrates the possibility of combining different levels of structural information to produce all-atom models suitable for quantitative MD simulations, which extends the range of systems amenable to the MD method and should enable exciting advances in our microscopic knowledge of biology.