Ion-induced free energy landscapes of Aβ33-42 peptide dimer in wet ionic liquids

The transitions between alpha-helix and beta-sheet conformation of A beta(33-42) peptide dimer in water and an aqueous solution of three ionic liquids (ILs) at two concentrations are investigated using umbrella sampling-based classical molecular dynamics simulations. The ionic liquids chosen for this study are Ethylammonium Mesylate (EAM), Ethylammonium Nitrate (EAN), and Triethylammonium Mesylate (TEAM). The average psi angle of the peptide backbone was used as the reaction coordinate to explore the free energy pathway of the transition. The secondary structure element values were calculated for peptide dimer along the reaction coordinate to probe the conformational changes during the transition between alpha-helix and beta-sheet conformations. We observe the alpha-helix conformation as the global minimum at low concentration of EAM and EAN IL and beta-sheet conformation as the global minimum at low concentration of TEAM as well as the high concentration of EAM, EAN, and TEAM ILs. The average numbers of intramolecular and intermolecular hydrogen bonds were calculated for the conformations corresponding to the free-energy minima: these numbers are in correlation with the secondary structure element values. The atom-atom radial distribution functions of cation, anion, and water around amide hydrogen and oxygen atoms of the peptide backbone were calculated to understand the peptide-IL interactions. The solvent-accessible surface area of the peptide was calculated to understand the exposure to the solvent during the transition. Finally, to understand the stability of conformations on the free-energy landscape, we calculated van der Waals and Coulomb interaction energies between peptide-cation, peptide anion, and peptide-water molecules. We find that the TEA cation in TEAM contributes more towards the vdWs and less towards Coulomb interactions with the peptide as compared to EA cation in EAM and EAN ILs, which results in destabilization of alpha-helix conformation in TEAM ILs. (C) 2020 Elsevier B.V. All rights reserved.