Exploring the Heterogeneous Dynamical Environment at the Interface of Aβ₄₂ Peptide in Aqueous Ionic Liquid Solution

Abstract

In this study, we have investigated the heterogeneous dynamical environment around an ensemble of full-length amyloid-β (Aβ 42 ) peptide monomers in binary aqueous solution containing the ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF 4 ] as a co-solvent. Atomistic molecular dynamics (MD) simulations have been employed with the aim of understanding the effect of the IL on the distribution of water molecules and IL components around distinct segments of the peptide. As compared to pure aqueous medium, locally heterogeneous restricted water motions at the interface have been spotted in the presence of the IL. Our calculations revealed faster diffusion of water molecules hydrating hydrophilic segments (Nterm and turn) as opposed to that around hydrophobic segments (hp1, hp2, and C-term). The extent of non-uniform restriction on the center-of-mass motions as well as the reorientation of water molecules and IL ions have been similarly affected in the binary IL−water solution. The effects of IL on the formation of hydrogen bond networks have been evident from the longer hydrogen bond relaxation time scales of peptide−water, with only a small fraction of peptide−anion hydrogen bonds contributing to the structural relaxation. Due to the size and shape factors, the increasingly sluggish dynamics of the IL components in the solvation shell can be attributed to a longer time scale for the onset of maximum dynamic heterogeneity. Interestingly, the water molecules around the polar segments of the peptide take longer to attain dynamic heterogeneity, which intensifies in the presence of IL. These calculations clearly suggest that electrostatic interaction plays a crucial role in water-mediated peptide−IL interaction, thereby shielding the surface from hydrophobic collapse and preventing possible further growth of the monomers into fibrils at higher peptide concentrations.

Conformational Properties of Aβ Peptide Oligomers in Aqueous Ionic Liquid Solution: Insights from Molecular Simulation Studies

“…30 In addition, site specific heterogeneous dynamics of water and IL components around the peptide monomers have also been studied. 31 In the present work, we have performed molecular dynamics (MD) simulations to probe the effects of binary aqueous solutions containing [BMIM][BF 4 ] as the IL on the conformational properties of Aβ 17−42 oligomers of different orders. Efforts have been made to gain microscopic insights into preferential distributions of the water and IL components at the interface and their influence on the structural distortions and stabilities of the oligomers.…”

“…Recently, we studied in detail the microscopic effects of [BMIM]­[BF 4 ] in aqueous solution on the conformational properties of an ensemble of Aβ 42 peptides in monomeric state . In addition, site specific heterogeneous dynamics of water and IL components around the peptide monomers have also been studied . In the present work, we have performed molecular dynamics (MD) simulations to probe the effects of binary aqueous solutions containing [BMIM]­[BF 4 ] as the IL on the conformational properties of Aβ 17–42 oligomers of different orders.…”