Effect of TFE on the Helical Content of AK17 and HAL-1 Peptides: Theoretical Insights into the Mechanism of Helix Stabilization

Abstract

Fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) are among the most frequently used cosolvents in experiment studies of peptides. They have significant effects on secondary structure and a particularly strong promotion of α-helix is induced by TFE. In this study we validated recently proposed force field parameters for TFE in molecular dynamics simulations with two model peptides-alanine-rich AK-17 and antimicrobial peptide halictine-1 (HAL-1). In the case of HAL-1, we characterized the effect of TFE on this peptide experimentally by ECD spectroscopy. Our TFE model in question reproduced the helix-promoting effect of TFE and provided insight into the mechanisms of TFE action on peptides. Our simulations confirmed the preferential interaction of TFE molecules with α-helices, although the TFE molecules accumulate in the vicinity of the peptides in various conformations. Moreover, we observed a significant effect of TFE on the thermodynamics of the helix-coil transition and a change in local conformational preferences in the unfolded (coil) state induced by TFE. In addition, our simulation-based analysis suggests that different mechanisms participate in helix stabilization in both model peptides in water and TFE solution. Our results thus support the picture of complex TFE action on peptides that is further diversified by the identity and intrinsic properties of the peptide.

Biomacromolecules enabled dendrite-free lithium metal battery and its origin revealed by cryo-electron microscopy

“…As natural ESM with inevitable defects is not suitable for battery systems, we tried to modify it by one-step TFEA solvothermal treatment to reduce the possible side reactions. Due to its low dielectric constant, TFEA can stabilize the natural structure of proteins, enhance electrostatic interactions, and particularly promote α-helix structure formation in peptides [50][51][52][53] . Attenuated total reflectance Fourier transformation infrared spectroscopy (ATR-FTIR) shows a blueshift of the characteristic bands for both amide I and amide II ( Supplementary Fig.…”

The Un(f)told Story of General Anesthesia

“…van der Waals interactions between the hydrophobic trifluoromethyl groups with apolar side chains permit water molecules associated with the peptide/protein backbone to be driven out …”

“… van der Waals interactions between the hydrophobic trifluoromethyl groups with apolar side chains permit water molecules associated with the peptide/protein backbone to be driven out The enhancement in intrahelical amide–amide H‐bonds by replacing helix‐destabilizing interfacial water molecules …”

“…It is pertinent to note that both the effectivity and relative contribution of these not‐well‐understood structure‐affecting mechanisms of fluoroalcohols are markedly dependent on the amino‐acid composition of the target sequences . The number and relative proportion of hydrophobic and disorder‐promoting polar/charged residues may seriously alter, amplify, or reduce the helix‐stabilization potency of fluoroalcohols.…”

Computing Free Energy Differences of Configurational Basins

“…Thanks to its modest size, alanine dipeptide has been often employed as a benchmark system 23 to verify sampling methods 19,21,24,25 or to evaluate the accuracy of force fields. 26 We apply the PLD scheme to calculate free energy differences between conformational states, or conformers, whose characterization in terms of φ and ψ angles is reported in Fig.…”