Accounting for Neighboring Residue Hydrophobicity in Diethylpyrocarbonate Labeling Mass Spectrometry Improves Rosetta Protein Structure Prediction.
Accounting for Neighboring Residue Hydrophobicity in Diethylpyrocarbonate Labeling Mass Spectrometry Improves Rosetta Protein Structure Prediction.
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DOI：
10.1021/jasms.1c00373
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发表时间：
2022-03-02
影响因子：
3.2
通讯作者：
Lindert S
中科院分区：
文献类型：
--
作者：
Biehn SE;Picarello DM;Pan X;Vachet RW;Lindert S
共价标记质谱法允许通过共价修饰和鉴定暴露的残基来阐明蛋白质结构。焦碳酸二乙酯（DEPC）是一种常用的共价标记试剂，通过标记赖氨酸、组氨酸、丝氨酸、苏氨酸和酪氨酸残基来深入了解结构。我们最近实现了一个Rosetta算法，该算法使用二进制DEPC标记数据来改进蛋白质结构预测工作。在这项工作中，我们改进了我们的建模工作，占丝氨酸，苏氨酸和酪氨酸残基的微环境中的相邻残基的疏水性水平，以获得更准确的估计的疏水邻居计数。这被纳入Rosetta功能，沿着考虑溶剂暴露的组氨酸和赖氨酸残基。总的来说，我们的新Rosetta评分项成功地确定了最佳评分模型，对于测试的七种基准蛋白质中的五种，其均方根偏差（RMSD）小于2 μ m。我们还开发了一个置信度指标来衡量预测成功的情况下，原生结构是不可用的。
Covalent labeling mass spectrometry allows for protein structure elucidation via covalent modification and identification of exposed residues. Diethylpyrocarbonate (DEPC) is a commonly used covalent labeling reagent that provides insight into structure through the labeling of lysine, histidine, serine, threonine, and tyrosine residues. We recently implemented a Rosetta algorithm that used binary DEPC labeling data to improve protein structure prediction efforts. In this work, we improved on our modeling efforts by accounting for the level of hydrophobicity of neighboring residues in the microenvironment of serine, threonine, and tyrosine residues to obtain a more accurate estimate of the hydrophobic neighbor count. This was incorporated into Rosetta functionality, along with considerations for solvent exposed histidine and lysine residues. Overall, our new Rosetta score term successfully identified best scoring models with less than 2 Å root-mean-squared deviations (RMSDs) for five of the seven benchmark proteins tested. We additionally developed a confidence metric to measure prediction success for situations in which a native structure is unavailable.
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