The Nest is a concave‐shaped structural motif in proteins formed by consecutive enantiomeric left‐handed (L) and right‐handed (R) helical conformation of the backbone. This important motif subsumes many turn and helix capping structures and binds electron‐rich ligands. Simple Nests are either RL or LR. Larger Nests (>2 residues long) may be RLR, LRL, RLRL, and so forth, being considered as composed of overlapping simple Nests. The larger Nests remain under‐explored despite their widely known contributions to protein function. In our study, we address whether the recurrence of enantiomeric geometry in the larger Nests constrains the peptide backbone such that distinct compositional and conformational preferences are seen compared to simple Nests. Our analysis reveals the critical role of the L helical torsion angle in the formation of larger Nests. This can be observed through the higher propensity of residue or secondary structure combinations in LR and LRL backbone conformation in comparison to RL or RLR, although LR/LRL is considerably lower by occurrence. We also find that the most abundant doublets and triplets in Nests have a propensity for particular secondary structures, suggesting a strong sequence‐structure relationship in the larger Nest. Overall, our analysis corroborates distinct features of simple and the larger Nests. Such insights would be helpful towards in‐vitro design of peptides and peptidomimetic studies.

中文翻译：

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蛋白质中较大的Nest图案的新面。

Nest是骨架的连续对映体左旋（L）和右旋（R）螺旋构象形成的蛋白质中的凹形结构基序。这个重要的基序包含许多匝和螺旋帽结构，并结合了富电子配体。简单嵌套是RL或LR。较大的嵌套（长度大于2个残基）可能是RLR，LRL，RLRL等，被认为是由重叠的简单嵌套组成。尽管大型巢对蛋白质功能的贡献广为人知，但仍未得到充分开发。在我们的研究中，我们研究了较大巢巢中对映异构体几何的重复是否约束了肽主链，因此与简单巢巢相比，可以看到不同的组成和构象偏好。我们的分析揭示了L螺旋扭转角在形成较大巢穴中的关键作用。与RL或RLR相比，这可以通过LR和LRL骨架构象中残基或二级结构组合的较高倾向来观察，尽管LR / LRL的发生率要低得多。我们还发现，巢中最丰富的双峰和三联体具有特定的二级结构倾向，这表明较大巢中的序列与结构之间存在很强的关系。总体而言，我们的分析证实了简单和较大的Nests的明显特征。这些见解将有助于肽的体外设计和拟肽研究。尽管LR / LRL发生时会大大降低。我们还发现，巢中最丰富的双峰和三联体具有特定的二级结构倾向，这表明较大巢中的序列与结构之间存在很强的关系。总体而言，我们的分析证实了简单和较大的Nests的明显特征。这些见解将有助于肽的体外设计和拟肽研究。尽管LR / LRL发生时会大大降低。我们还发现，巢中最丰富的双峰和三联体具有特定的二级结构倾向，这表明较大巢中的序列与结构之间存在很强的关系。总体而言，我们的分析证实了简单和较大的Nests的明显特征。这些见解将有助于肽的体外设计和拟肽研究。