During the last two decades, numerous observed data obtained by various physical techniques, also supported by molecular modeling approaches, have highlighted the structuring features of tripeptides, as well as their aggregation properties. Herein, we focus on the structural dynamics of four trimers, i.e., Gly-Gly-Gly, Gly-Ala-Gly, Ala-Ala-Ala and Ala-Phe-Ala, in an aqueous environment. Density functional theory calculations (DFT) were carried out to assess the stability of four types of secondary structures, i.e., β-strand, polyproline-II (pP-II), α-helix and γ-turn, of which the formation had been described in these tripeptides. Both implicit and explicit hydration effects were analyzed on the conformational and energetic features of trimers. It has been shown that the use of M062X functional (versus B3LYP) improve the stability of intramolecular H-bonds, especially in inverse γ-turn structures, as well as the energetic and conformational equilibrium in all tripeptides. Explicit hydration reflected by the presence of five water molecules around the backbone polar sites (NH₃⁺, N–H, CO and NH₂) considerably changes the conformational landscapes of the trimers. Characteristic intramolecular and intermolecular interactions evidenced by the calculations, were emphasized.

在过去的二十年中，通过各种物理技术获得的大量观测数据（也得到分子建模方法的支持）突出了三肽的结构特征及其聚集特性。在本文中，我们集中在水性环境中四个三聚体，即Gly-Gly-Gly，Gly-Ala-Gly，Ala-Ala-Ala和Ala-Phe-Ala的结构动力学。进行密度泛函理论计算（DFT）以评估四种类型的二级结构的稳定性，即β-链，聚脯氨酸-II（pP-II），α-螺旋和γ-转角，这些三肽中已描述了它们的形成。分析了三聚体的构象和能量特征，隐含和显着的水合效应。已经显示，使用M062X官能团（相对于B3LYP）可改善分子内H键的稳定性，尤其是在反向γ-转角结构中，以及所有三肽中的能量和构象平衡。骨干极性位点（NH ₃ ⁺，NH– ，CO和NH ₂）周围五个水分子的存在反映出明显的水合作用，极大地改变了三聚体的构象。强调了通过计算证明的分子内和分子间相互作用的特征。