The Analytical Flory Random Coil Is a Simple-to-Use Reference Model for Unfolded and Disordered Proteins
The Analytical Flory Random Coil Is a Simple-to-Use Reference Model for Unfolded and Disordered Proteins
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DOI：
10.1021/acs.jpcb.3c01619
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发表时间：
2023-05-18
影响因子：
3.3
通讯作者：
Holehouse, Alex S. S.
中科院分区：
文献类型：
--
作者：
Alston, Jhullian J. J.;Ginell, Garrett M. M.;Holehouse, Alex S. S.
变性的、未折叠的和本质上无序的蛋白质（此处统称为未折叠蛋白质）可以使用分析聚合物模型来描述。这些模型捕获各种聚合物特性，并且可以拟合模拟结果或实验数据。然而，模型参数通常需要用户做出决定，这使得它们对于数据解释很有用，但作为独立参考模型的适用性不太明确。在这里，我们使用多肽的全原子模拟结合聚合物尺度理论来参数化表现为理想链的未折叠多肽的分析模型（nu = 0.50）。该模型被我们称为分析型 Floryrandom 线圈 (AFRC)，仅需要氨基酸序列作为输入，并提供对全局和局部构象顺序参数的概率分布的直接访问。该模型定义了一个特定的参考状态，可以对实验和计算结果进行比较和标准化。作为概念验证，我们使用 AFRC 来识别无序蛋白质模拟中序列特异性的分子内相互作用。我们还使用 AFRC 来背景化从先前发表的无序蛋白质小角度 X 射线散射实验中获得的 145 个不同回转半径的精选集。 AFRC 作为独立软件包实现，也可通过 Google Colab 笔记本使用。总之，AFRC 提供了一个简单易用的参考聚合物模型，可以指导直觉并帮助解释实验或模拟结果。
Denatured, unfolded, and intrinsically disordered proteins(collectivelyreferred to here as unfolded proteins) can be described using analyticalpolymer models. These models capture various polymeric propertiesand can be fit to simulation results or experimental data. However,the model parameters commonly require users' decisions, makingthem useful for data interpretation but less clearly applicable asstand-alone reference models. Here we use all-atom simulations ofpolypeptides in conjunction with polymer scaling theory to parameterizean analytical model of unfolded polypeptides that behave as idealchains (nu = 0.50). The model, which we call the analytical Floryrandom coil (AFRC), requires only the amino acid sequence as inputand provides direct access to probability distributions of globaland local conformational order parameters. The model defines a specificreference state to which experimental and computational results canbe compared and normalized. As a proof-of-concept, we use the AFRCto identify sequence-specific intramolecular interactions in simulationsof disordered proteins. We also use the AFRC to contextualize a curatedset of 145 different radii of gyration obtained from previously publishedsmall-angle X-ray scattering experiments of disordered proteins. TheAFRC is implemented as a stand-alone software package and is alsoavailable via a Google Colab notebook. In summary, the AFRC providesa simple-to-use reference polymer model that can guide intuition andaid in interpreting experimental or simulation results.