Theoretical Neurosciences Group, Institute De Neurosciences Des Systems, Aix-Marseille University, France.
Department of Microbiology, Asutosh College (affiliated to University of Calcutta), Kolkata 700026, India.
Biochim Biophys Acta Proteins Proteom. 2020 Oct;1868(10):140474. doi: 10.1016/j.bbapap.2020.140474. Epub 2020 Jun 21.
Intrinsically disordered proteins (IDP) serve as one of the key components in the global proteome. In contrast to globular proteins, they harbor an enormous amount of physical flexibility enforcing them to be retained in conformational ensembles rather than stable folds. Previous studies in an aligned direction have revealed the importance of transient dynamical phenomena like that of salt-bridge formation in IDPs to support their physical flexibility and have further highlighted their functional relevance. For this characteristic flexibility, IDPs remain amenable and accessible to different ordered binding partners, supporting their potential multi-functionality. The current study further addresses this complex structure-functional interplay in IDPs using phase transition dynamics to conceptualize the underlying (avalanche type) mechanism of their being distributed across and hopping around degenerate structural states (conformational ensembles). For this purpose, extensive molecular dynamics simulations have been done and the data analyzed from a statistical physics perspective. Investigation of the plausible scope of 'self-organized criticality' (SOC) to fit into the complex dynamics of IDPs was found to be assertive, relating the conformational degeneracy of these proteins to their functional multiplicity. In accordance with the transient nature of 'salt-bridge dynamics', the study further uses it as a probe to explain the structural basis of the proposed criticality in the conformational phase transition among self-similar groups in IDPs. The analysis reveal scale-invariant self-similar fractal geometries in the structural conformations of different IDPs. The insights from the study has the potential to be extended further to benefit structural tinkering of IDPs in their functional characterization and drugging.
无定形蛋白质（IDP）是全球蛋白质组的关键组成部分之一。与球状蛋白质不同，它们具有大量的物理灵活性，使它们保留在构象集合中而不是稳定的折叠中。以前在对齐方向上的研究揭示了 IDP 中瞬态动力学现象（如盐桥形成）的重要性，以支持其物理灵活性，并进一步强调了它们的功能相关性。由于这种特征灵活性，IDP 仍然可以与不同的有序结合伙伴结合，支持它们的潜在多功能性。本研究进一步使用相变动力学来研究 IDP 中的这种复杂结构-功能相互作用，以概念化它们在简并结构状态（构象集合）之间分布和跳跃的潜在（雪崩类型）机制。为此，进行了广泛的分子动力学模拟，并从统计物理的角度分析了数据。研究发现，“自组织临界性”（SOC）的合理范围适合 IDP 的复杂动力学，将这些蛋白质的构象简并性与其功能多样性联系起来。根据“盐桥动力学”的瞬态性质，该研究进一步将其用作探针，以解释 IDP 中自相似组之间构象相变中拟议临界性的结构基础。分析揭示了不同 IDP 结构构象中具有标度不变的自相似分形几何形状。该研究的结果有可能进一步扩展到 IDP 的功能表征和药物设计中的结构调整中受益。
