Refining Disordered Peptide Ensembles with Computational Amide I Spectroscopy: Application to Elastin-Like Peptides.
Refining Disordered Peptide Ensembles with Computational Amide I Spectroscopy: Application to Elastin-Like Peptides.
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利用计算酰胺 I 光谱精炼无序肽整体：在弹性蛋白样肽中的应用。
DOI：
10.1021/acs.jpcb.6b08678
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Tokmakoff,Andrei
中科院分区：
文献类型：
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作者：
Reppert,Mike;Roy,AnishR;Tempkin,JeremyOB;Dinner,AaronR;Tokmakoff,Andrei
固有无序蛋白质（IDP）系综的表征是复杂的固有的异质性和许多常见的实验技术的功能不佳时，适用于IDP。出于这个原因，开发替代结构工具探测IDP合奏吸引了相当大的关注。在这里，我们描述了我们最近的工作，在开发实验和计算工具，用于表征IDP合奏使用酰胺I（骨架羰基伸缩）振动光谱。在这种方法中，同位素标记的酰胺键的红外（IR）吸收频率探测其局部静电环境和结构。经验频率图使我们能够使用这种光谱数据作为原子结构模型的直接实验测试。我们将这些方法应用于一个家庭的短弹性蛋白样肽（ELP），片段的弹性蛋白的基础上周围的Pro-Gly转基序特征的弹性部分的完整的蛋白质。使用最大熵分析，适用于从实验光谱的限制，加权预测光谱的分子动力学（MD）合奏，我们发现，肽与Ala或瓦尔侧链前的Pro-Gly转单位表现出更强的倾向于扩展结构比做Gly-Pro-Gly基序，这表明了空间相互作用在调整弹性蛋白的分子特性的重要作用。
The characterization of intrinsically disordered protein (IDP) ensembles is complicated both by inherent heterogeneity and by the fact that many common experimental techniques function poorly when applied to IDPs. For this reason, the development of alternative structural tools for probing IDP ensembles has attracted considerable attention. Here we describe our recent work in developing experimental and computational tools for characterizing IDP ensembles using Amide I (backbone carbonyl stretch) vibrational spectroscopy. In this approach, the infrared (IR) absorption frequencies of isotope-labeled amide bonds probe their local electrostatic environments and structures. Empirical frequency maps allow us to use this spectroscopic data as a direct experimental test of atomistic structural models. We apply these methods to a family of short elastin-like peptides (ELPs), fragments of the elastin protein based around the Pro-Gly turn motif characteristic of the elastomeric segments of the full protein. Using a maximum entropy analysis that applies constraints from experimental spectra to weighting predicted spectra from molecular dynamics (MD) ensembles, we find that peptides with Ala or Val side chains preceding the Pro-Gly turn unit exhibit a stronger tendency toward extended structures than do Gly-Pro-Gly motifs, suggesting an important role for steric interactions in tuning the molecular properties of elastin.