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

• Published in: Journal of molecular graphics & modelling 2021-01, Vol.102, p.107790-107790, Article 107790
• Main Authors: Hernández, Belén, Pflüger, Fernando, Kruglik, Sergei G., Ghomi, Mahmoud
• Format: Article
• Language: English
• Subjects: Computer Science; Conformational equilibrium; Density functional theory calculations; Extended chain; Polyproline-II; Tripeptides; α-helix; β-strand; γ-turn
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2020.107790

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. [Display omitted] •The energetic and conformational features of four tripeptides (GGG, GAG, AAA and AFA) were analyzed by DFT calculations.•The stability of different types of secondary structures (β-strand, helix, pP-II, γ-turn) was analyzed.•Both implicit and explicit hydration effects were analyzed on the conformational equilibrium of the tripeptides.•The superiority of M062X functional (versus B3LYP) was discussed upon the structural stability of calculated conformers.•Intramolecular and intermolecular interactions as evidenced by calculations were emphasized.