Multiconformational analysis of tripeptides upon consideration of implicit and explicit hydration effects

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., beta-strand, polyproline-II (pP-II), alpha-helix and gamma-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 g-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 (NH3thorn, N-H, C=O and NH2) considerably changes the conformational landscapes of the trimers. Characteristic intramolecular and intermolecular interactions evidenced by the calculations, were emphasized. (c) 2020 Elsevier Inc. All rights reserved.

Automated summary

This article focuses on the structural dynamics of four trimers in an aqueous environment and evaluates the stability of their secondary structures using density functional theory calculations. The study demonstrates that the choice of functional affects the stability of intramolecular hydrogen bonds and conformational equilibrium in the trimers, while explicit hydration has a significant impact on the conformational landscapes of the peptides.