Department of Chemistry and Biochemistry, Denison University, Granville, OH 43023, USA.
Department of Chemistry and Biochemistry, Ohio State University, 2114 Newman & Wolfrom Laboratory, 100 W. 18(th) Avenue, Columbus, OH 43210, USA.
Structure. 2022 Feb 3;30(2):313-320.e3. doi: 10.1016/j.str.2021.10.006. Epub 2021 Nov 4.
Hydrogen-deuterium exchange (HDX) measured by nuclear magnetic resonance (NMR) provides structural information for proteins relating to solvent accessibility and flexibility. While this structural information is beneficial, the data cannot be used exclusively to elucidate structures. However, the structural information provided by the HDX-NMR data can be supplemented by computational methods. In previous work, we developed an algorithm in Rosetta to predict structures using qualitative HDX-NMR data (categories of exchange rate). Here we expand on the effort, and utilize quantitative protection factors (PFs) from HDX-NMR for structure prediction. From observed correlations between PFs and solvent accessibility/flexibility measures, we present a scoring function to quantify the agreement with HDX data. Using a benchmark set of 10 proteins, an average improvement of 5.13 Å in root-mean-square deviation (RMSD) is observed for cases of inaccurate Rosetta predictions. Ultimately, seven out of 10 predictions are accurate without including HDX data, and nine out of 10 are accurate when using our PF-based HDX score.
氢氘交换（HDX）通过核磁共振（NMR）测量为蛋白质提供了与溶剂可及性和柔韧性相关的结构信息。虽然这些结构信息是有益的，但数据不能单独用于阐明结构。然而，HDX-NMR 数据提供的结构信息可以通过计算方法来补充。在以前的工作中，我们在 Rosetta 中开发了一种算法，使用定性的 HDX-NMR 数据（交换率类别）来预测结构。在这里，我们进一步扩展了这项工作，并利用 HDX-NMR 的定量保护因子（PF）进行结构预测。从观察到的 PF 与溶剂可及性/柔韧性测量之间的相关性，我们提出了一种评分函数来量化与 HDX 数据的一致性。使用 10 个蛋白质的基准集，对于罗塞塔不准确预测的情况，观察到均方根偏差（RMSD）平均提高了 5.13Å。最终，在不包含 HDX 数据的情况下，有 7 个预测是准确的，而在使用我们基于 PF 的 HDX 评分时，有 9 个预测是准确的。
