Underlying mechanism of bio-nano-machine investigated by massive molecular dynamics method

细菌鞭毛细丝是由单个蛋白质鞭毛蛋白组成的大分子组装体。细菌的游动是由鞭毛电机扭矩引起的左旋和右旋超级线圈之间的丝的构象转变控制的。我们提出了一个大规模的分子动力学模拟，成功地构建了与各种实验数据一致的原子级超线圈结构，并进一步阐明了多态超线圈的详细潜在分子机制。我们发现，以下三种类型的相互作用是理解超卷曲机制的关键。在各种超级线圈结构的亚基之间总是保持“永久”相互作用。可变亲水或疏水残基对之间形成“滑动”相互作用，允许亚基间剪切而不发生大的能量变化。“开关”相互作用的形成和断裂分别稳定了亚基间和亚基内的相互作用。我们得出结论，多态超卷曲是由于它们之间的能量挫折。超级线圈之间的过渡是通过“转换和放松”机制实现的：灯丝结构在几何上快速转换，然后通过重新安排相互作用慢慢放松到能量亚稳定状态。

Bacterial flagellar filament is a macromolecular assembly consisting of single protein, flagellin. Bacterial swimming is controlled by the conformational transitions of this filament between left- and right-handed supercoils induced by the flagellar motor torque. We present that a massive molecular dynamics simulation was successful in constructing the atomic-level supercoil structures consistent to various experimental data and further in elucidating the detailed underlying molecular mechanisms of the polymorphic supercoiling. We have found that the following three types of interactions are keys to understanding the supercoiling mechanism. "Permanent" interactions are always maintained between subunits in the various supercoil structures. "Sliding" interactions are formed between variable hydrophilic or hydrophobic residue pairs, allowing intersubunit shear without large change in energy. The formation and breakage of "switch" interactions stabilize inter- and intrasubunit interactions, respectively. We conclude that polymorphic supercoiling is due to the energy frustration between them. The transition between supercoils is achieved by a "transform and relax" mechanism : the filament structure is geometrically transformed rapidly and then slowly relaxes to energetically meta-stable states by rearranging interactions.