Institute of Molecular Modeling and Simulation (MMS), University of Natural Resources and Life Sciences, Vienna, Austria.
Phys Chem Chem Phys. 2024 Sep 18;26(36):23856-23870. doi: 10.1039/d4cp02484b.
Nuclear magnetic resonance (NMR) is an important method for structure elucidation of proteins, as it is an easily accessible and well understood method. To characterize intrinsically disordered proteins (IDPs) using computational models it is often necessary to analyze and integrate calculated observables with measurements derived from solution NMR experiments. In this case study, we investigate whether and which chemical shifts of the proline-rich region of Tau protein (residues 210-240) offer information about the conformational state to distinguish two different microscopic conformers. Using multiple computational methods, the chemical shifts of these two conformationally distinct structures are calculated. The different methods are compared regarding their ability to compute chemical shifts that are sensitive to conformational change. The analysis of the data shows significant differences between the available methods and gives suggestions for an improved pathway for ensemble reweighting. Nevertheless, the variation in the chemical shifts which are predicted for configurations that are commonly considered to belong to the same conformation is such that this obscures a comparison between distinct conformations. Conformational sensitivity is found for up to ∼26% of calculated chemical shifts. It is found to be unrelated to the atom element and has a minor relationship with the change in the corresponding dihedral angle.
核磁共振（NMR）是一种用于蛋白质结构解析的重要方法，因为它是一种易于访问且易于理解的方法。为了使用计算模型对无规卷曲蛋白质（IDP）进行特征描述，通常需要分析和整合计算得出的可观测值与来自溶液 NMR 实验的测量值。在本案例研究中，我们研究了富含脯氨酸的 Tau 蛋白（残基 210-240）区域的化学位移是否以及在何种程度上提供了关于构象状态的信息，以区分两种不同的微观构象。使用多种计算方法，计算了这两种构象上不同结构的化学位移。比较了不同方法在计算对构象变化敏感的化学位移方面的能力。数据分析表明，不同方法之间存在显著差异，并为改进整体重新加权的途径提供了建议。然而，对于通常被认为属于同一构象的配置的预测化学位移的变化如此之大，以至于掩盖了不同构象之间的比较。在高达约 26%的计算化学位移中发现了构象敏感性。它与原子元素无关，与相应二面角的变化也只有轻微的关系。
