Alston Jhullian J, Ginell Garrett M, Soranno Andrea, Holehouse Alex S
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO, USA.
bioRxiv. 2023 Mar 13:2023.03.12.531990. doi: 10.1101/2023.03.12.531990.
Denatured, unfolded, and intrinsically disordered proteins (collectively referred to here as unfolded proteins) can be described using analytical polymer models. These models capture various polymeric properties and can be fit to simulation results or experimental data. However, the model parameters commonly require users' decisions, making them useful for data interpretation but less clearly applicable as stand-alone reference models. Here we use all-atom simulations of polypeptides in conjunction with polymer scaling theory to parameterize an analytical model of unfolded polypeptides that behave as ideal chains (ν = 0.50). The model, which we call the analytical Flory Random Coil (AFRC), requires only the amino acid sequence as input and provides direct access to probability distributions of global and local conformational order parameters. The model defines a specific reference state to which experimental and computational results can be compared and normalized. As a proof-of-concept, we use the AFRC to identify sequence-specific intramolecular interactions in simulations of disordered proteins. We also use the AFRC to contextualize a curated set of 145 different radii of gyration obtained from previously published small-angle X-ray scattering experiments of disordered proteins. The AFRC is implemented as a stand-alone software package and is also available via a Google colab notebook. In summary, the AFRC provides a simple-to-use reference polymer model that can guide intuition and aid in interpreting experimental or simulation results.
变性、解折叠和内在无序的蛋白质（在此统称为解折叠蛋白）可以用分析性聚合物模型来描述。这些模型捕捉了各种聚合物性质，并且可以与模拟结果或实验数据相拟合。然而，模型参数通常需要用户来决定，这使得它们对数据解释很有用，但作为独立的参考模型应用起来不太明确。在这里，我们将多肽的全原子模拟与聚合物标度理论结合起来，对表现为理想链（ν = 0.50）的解折叠多肽的分析模型进行参数化。我们将这个模型称为分析性弗洛里无规线团（AFRC），它只需要氨基酸序列作为输入，并能直接获取全局和局部构象序参量的概率分布。该模型定义了一个特定的参考状态，实验和计算结果可以与之进行比较和归一化。作为概念验证，我们使用AFRC在无序蛋白模拟中识别序列特异性分子内相互作用。我们还使用AFRC对从先前发表的无序蛋白小角X射线散射实验中获得的一组145个不同的回转半径进行情境化分析。AFRC被实现为一个独立的软件包，也可以通过谷歌Colab笔记本获得。总之，AFRC提供了一个易于使用的参考聚合物模型，可以引导直觉并有助于解释实验或模拟结果。
