The compound 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) is a versatile fluorophore widely used in Förster resonance energy transfer (FRET) spectroscopy studies due to its remarkable sensitivity, enabling precise donor–acceptor distance measurements, even for short peptides. Integrating time-resolved and FRET spectroscopies with molecular dynamics simulations provides a robust approach to unravel the structure and dynamics of biopolymers in a solution. This study investigates the structural behavior of three octapeptide variants: Trp-(Gly-Ser)3-Dbo, Trp-(GlyGly)3-Dbo, and Trp-(SerSer)3-Dbo, where Dbo represents the DBO-containing modified aspartic acid, using molecular dynamics simulations. Glycine- and serine-rich amino acid fragments, common in flexible protein regions, play essential roles in functional properties. Results show excellent agreement between end-to-end distances, orientational factors from simulations, and the available experimental and theoretical data, validating the reliability of the GROMOS force field model. The end-to-end distribution, modeled using three Gaussian distributions, reveals a complex shape, confirmed by cluster analysis highlighting a limited number of significant conformations dominating the peptide landscape. All peptides predominantly adopt a disordered state in the solvent, yet exhibit a compact shape, aligning with the model of disordered polypeptide chains in poor solvents. Conformations show marginal dependence on chain composition, with Ser-only chains exhibiting slightly more elongation. This study enhances our understanding of peptide behavior, providing valuable insights into their structural dynamics in solution.

中文翻译：

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2,3-二氮杂双环[2.2.2]oct-2-ene荧光团标记甘氨酸/丝氨酸八肽的分子动力学模拟研究

化合物 2,3-二氮杂双环[2.2.2]辛-2-烯 (DBO) 是一种多功能荧光团，因其卓越的灵敏度而广泛用于福斯特共振能量转移 (FRET) 光谱研究，可实现精确的供体-受体距离测量，即使是短肽。将时间分辨光谱和 FRET 光谱与分子动力学模拟相结合，提供了一种稳健的方法来揭示溶液中生物聚合物的结构和动力学。本研究研究了三种八肽变体的结构行为：Trp-(Gly-Ser)3-Dbo、Trp-(GlyGly)3-Dbo 和 Trp-(SerSer)3-Dbo，其中 Dbo 代表含有 DBO 的修饰天冬氨酸酸，使用分子动力学模拟。富含甘氨酸和丝氨酸的氨基酸片段常见于柔性蛋白质区域，在功能特性中发挥着重要作用。结果显示，端到端距离、模拟的方向因素以及可用的实验和理论数据之间具有良好的一致性，验证了 GROMOS 力场模型的可靠性。使用三个高斯分布建模的端到端分布揭示了复杂的形状，通过聚类分析证实，突出显示了主导肽景观的有限数量的重要构象。所有肽在溶剂中主要呈现无序状态，但表现出紧凑的形状，与不良溶剂中无序多肽链的模型一致。构象显示出对链组成的边际依赖性，仅 Ser 的链表现出稍微更多的伸长。这项研究增强了我们对肽行为的理解，为了解其在溶液中的结构动力学提供了宝贵的见解。