The need for accurate and efficient force fields for modeling 3D structures of macrobiomolecules and in particular intrinsically disordered proteins (IDPs) has increased with recent findings to associate IDPs and human diseases. However, most conventional protein force fields and recent IDP-specific force fields are limited in reproducing accurate structural features of IDPs. Here, we present an environmental specific precise force field (ESFF1) based on CMAP corrections of 71 different sequence environments to improve the accuracy and efficiency of MD simulation for both IDPs and folded proteins. MD simulations of 84 different short peptides, IDPs, and structured proteins show that ESFF1 can accurately reproduce spectroscopic properties for different peptides and proteins whether they are disordered or ordered. The successful ab initio folding of five fast-folding proteins further supports the reliability of ESFF1. The extensive analysis documented here shows that ESFF1 is able to achieve a reasonable balance between ordered and disordered states in protein simulations.

中文翻译：

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本质上无序和有序蛋白质的环境特异性力场。

随着最近将 IDP 与人类疾病联系起来的发现，对用于对大生物分子（特别是本质无序蛋白质 (IDP)）的 3D 结构进行建模的准确有效的力场的需求不断增加。然而，大多数传统的蛋白质力场和最近的 IDP 特异性力场在再现 IDP 的准确结构特征方面受到限制。在这里，我们提出了基于 71 个不同序列环境的 CMAP 校正的环境特定精确力场 (ESFF1)，以提高 IDP 和折叠蛋白的 MD 模拟的准确性和效率。对 84 种不同的短肽、IDP 和结构蛋白的 MD 模拟表明，ESFF1 可以准确地再现不同肽和蛋白质的光谱特性，无论它们是无序的还是有序的。五种快速折叠蛋白的成功从头开始折叠进一步支持了 ESFF1 的可靠性。这里记录的广泛分析表明，ESFF1 能够在蛋白质模拟中实现有序状态和无序状态之间的合理平衡。