On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures.
On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures.
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DOI：
10.1002/pro.2896
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Woolfson DN
中科院分区：
文献类型：
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作者：
Bartlett GJ;Woolfson DN
蛋白质结构的稳定是由各种非共价相互作用（NCI），包括疏水作用，氢键，静电力和货车范德华相互作用。我们对国家信息中心的贡献以及它们之间的相互作用的了解仍然是不完整的。这对NCI的计算建模以及我们理解和预测蛋白质结构、稳定性和功能的能力具有影响。一个考虑因素是满足骨架原子产生的NCI的全部潜力。最常见的是，位于α-螺旋和β-折叠内的骨架-羰基氧原子被描述为形成单个氢键。然而，对于这些原子中的每一个，都有两个孤对电子需要满足。为了探索这一点，我们使用操作几何定义从一组高分辨率蛋白质结构和水中相关的分子动力学模拟中生成骨架羰基氧原子的NCI清单。在我们的分析中，我们包括了最近受到重视但较弱的NCI，例如n→π* 相互作用，Cα-H键和甲基-H键。这些数据表明，所有蛋白质都是平衡的动态系统，大多数骨架羰基氧原子在大多数时间都由两个NCI满足。NCI的组合可能与二级结构类型相关，尽管与传统的α和β结构模型有细微的不同。此外，我们还发现了欠满意和过满意的羰基氧原子的例子，并确定了这些二级结构基序中的序列依赖性和序列无关性。我们的分析提供了对蛋白质结构和稳定性的这些贡献者的更详细的理解，这将用于蛋白质建模，工程和设计。
Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals’ interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone‐carbonyl oxygen atoms located within α‐helices and β‐sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone‐carbonyl oxygen atoms from a set of high‐resolution protein structures and associated molecular‐dynamics simulations in water. We included more‐recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα‐H bonds and methyl‐H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone‐carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α‐ and β‐structure. In addition, we find examples of under‐ and over‐satisfied carbonyl‐oxygen atoms, and we identify both sequence‐dependent and sequence‐independent secondary‐structural motifs in which these reside. Our analysis provides a more‐detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design.