论文标题
具有远距离互动的自组织网络：$α$和$β$ tubulin的串联达尔文人的演变
Self-Organized Networks with Long-Range Interactions: Tandem Darwinian Evolution of $α$ and $β$ Tubulin
论文作者
论文摘要
细胞骨架是基于聚合蛋白的自组织网络：肌动蛋白，微管蛋白，并由运动蛋白（例如肌球蛋白，驱动蛋白和动力蛋白）驱动。他们积极的达尔文进化使他们能够接近优化的功能（自组织的批判性）。我们的理论分析使用水产波来识别和对比聚合$α$和$β$微管蛋白单体之间的功能差异，这些单体的长度和二级结构相似，并且具有无法区分的系统发育树。我们展示了进化如何改善水驱动的灵活性，特别是对于$α$微管蛋白，从而促进了异二聚体微管组件，与最近的原子模拟和拓扑模型一致。我们得出的结论是，系统发育分析未能识别特定于功能特定的达尔文式进化，这是由于20世纪的技术局限性引起的。使用基于热力学缩放和水力学模块化平均的21世纪定量数学方法克服了这些方法。我们最令人惊讶的结果是鉴定了大级别集合，尤其是在疏水极端，同时具有热力学的一阶和二阶缩放水波。我们的计算包括分形所描述的明确的远距离水 - 蛋白质相互作用。我们还建议对大型蛋白质药物开发成本进行急需的纠正措施。
Cytoskeletons are self-organized networks based on polymerized proteins: actin, tubulin, and driven by motor proteins, such as myosin, kinesin and dynein. Their positive Darwinian evolution enables them to approach optimized functionality (self-organized criticality). Our theoretical analysis uses hydropathic waves to identify and contrast the functional differences between the polymerizing $α$ and $β$ tubulin monomers, which are similar in length and secondary structures, as well as having indistinguishable phylogenetic trees. We show how evolution has improved water-driven flexibility especially for $α$ tubulin, and thus facilitated heterodimer microtubule assembly, in agreement with recent atomistic simulations and topological models. We conclude that the failure of phylogenetic analysis to identify functionally specific positive Darwinian evolution has been caused by 20th century technical limitations. These are overcome using 21st century quantitative mathematical methods based on thermodynamic scaling and hydropathic modular averaging. Our most surprising result is the identification of large level sets, especially in hydrophobic extrema, with both thermodynamically first- and second-order scaled water waves. Our calculations include explicitly long-range water-protein interactions described by fractals. We also suggest a much-needed corrective for large protein drug development costs.
