标题： 当$B_2$不够时：评估简单指标预测内在无序蛋白质相分离的能力 显示英文标题

标题： When $B_2$ is Not Enough: Evaluating Simple Metrics for Predicting Phase Separation of Intrinsically Disordered Proteins

摘要： 理解并预测固有无序蛋白质（IDPs）的相行为在许多生物过程中具有重要意义。然而，有效表征相行为及其对蛋白质一级序列的复杂依赖性仍然具有挑战性。在本研究中，我们评估了几种简单的计算指标的有效性，以量化单组分IDP溶液发生相分离的倾向；所考虑的具体指标包括单链回转半径、第二维里系数以及一种新提出的称为消耗密度的量。每个指标都是通过粗粒度分子动力学模拟计算的，针对2,034个IDP序列。利用机器学习，我们分析这些数据以了解序列特征如何与每个指标的预测性能相关，并深入了解它们各自的优缺点。确定消耗密度是一个广泛有用的指标，它结合了简单性、低计算成本和准确性；它还提供了一个连续的度量，在相分离和非相分离序列中都具有信息量。此外，该指标在提高IDP系统其他性质的预测能力方面显示出前景。这项工作通过超越二元分类扩展了现有文献，这在快速筛选相行为或预测与IDP相关的系统其他性质时可能有用。 显示英文摘要

摘要： Understanding and predicting the phase behavior of intrinsically disordered proteins (IDPs) is of significant interest due to their role in many biological processes. However, effectively characterizing phase behavior and its complex dependence on protein primary sequence remains challenging. In this study, we evaluate the efficacy of several simple computational metrics to quantify the propensity of single-component IDP solutions to phase separate; specific metrics considered include the single-chain radius of gyration, the second virial coefficient, and a newly proposed quantity termed the expenditure density. Each metric is computed using coarse-grained molecular dynamics simulations for 2,034 IDP sequences. Using machine learning, we analyze this data to understand how sequence features correlate with the predictive performance of each metric and to develop insight into their respective strengths and limitations. The expenditure density is determined to be a broadly useful metric that combines simplicity, low computational cost, and accuracy; it also provides a continuous measure that remains informative across both phase-separating and non-phase-separating sequences. Additionally, this metric shows promise in its ability to improve predictions of other properties for IDP systems. This work extends existing literature by advancing beyond binary classification, which can be useful for rapidly screening phase behavior or predicting other properties of IDP-related systems.