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Tubulin's response to external electric fields by molecular dynamics simulations

机译:微管蛋白通过分子动力学模拟对外部电场的反应

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摘要

Tubulin heterodimers are the building blocks of microtubules and disruption of their dynamics is exploited in the treatment of cancer. Electric fields at certain frequencies and magnitudes are believed to do the same. Here, the tubulin dimer's response to external electric fields was determined by atomistic simulation. External fields from 50 to 750 kV/cm, applied for 10 ns, caused significant conformational rearrangements that were dependent upon the field's directionality. Charged and flexible regions, including the α:H1-B2 loop, β:M-loop, and C-termini, were susceptible. Closer inspection of the α:H1-B2 loop in lower strength fields revealed that these effects were consistent and proportional to field strength, and the findings indicate that external electric fields modulate the stability of microtubules through conformational changes to key loops involved in lateral contacts. We also find evidence that tubulin's curvature and elongation are affected, and external electric fields may bias tubulin towards depolymerization.
机译:微管蛋白的异二聚体是微管的结构块,并且在治疗癌症时利用它们的动态破坏。据信,某些频率和大小的电场可以这样做。这里,通过原子模拟确定小管蛋白二聚体对外部电场的响应。施加10 ns的50至750 kV / cm的外部领域导致了依赖于现场方向性的重要构象重排。带电和灵活的区域,包括α:H1-B2环,β:M环和C-Termini易感。较近强度场中的α:H1-B2环的检查显示,这些效果是一致的和与场强的成比例,并且该研究结果表明外部电场通过构象改变来调节微管的稳定性,这是横向触点所涉及的关键环的键环的稳定性。我们还发现有证据表明微管蛋白的曲率和伸长率受到影响,并且外部电场可以偏向解聚合。

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