Impact of sodium dodecyl sulfate, cetyltrimethylammonium chloride and octyl glucoside surfactants on Aβ dimer conformations: A multiscale approach with MD simulations

Abstract

This research investigates the effects of an anionic surfactant, sodium dodecyl sulfate (SDS), a cationic surfactant, cetyltrimethylammonium chloride (CTAC), and a nonionic surfactant, octyl glucoside (OG), on the conformation of beta-amyloid peptide dimer using molecular dynamics simulations to decipher the molecular mechanisms underlying these interactions and their effects on Aβ aggregation and toxicity in Alzheimer’s disease. Four simulation models were crafted, each housing a beta-amyloid peptide dimer, with three models incorporating 60 CTAC, 80 SDS, and 50 OG molecules to surpass the critical micelle concentration. Key findings include significant impacts of SDS, CTAC, and OG on the conformational dynamics of Aβ peptides as evidenced by RMSD and RMSF analyses. SDS notably increased the RMSF of residues 1–10 and had a pronounced effect on the C-termini, disrupting the critical salt bridge between aspartic acid 23 and lysine 28, associated with reduced peptide toxicity. Additionally, SDS disrupted more hydrogen bonds and hydrophobic interactions between the monomers of the Aβ dimer, predominantly in the C-termini region. Free Energy Landscape analysis revealed significant structural changes in the Aβ dimer in the presence of surfactants, with varying distributions of surfactant aggregates. Binding free energy calculations using MM-PBSA demonstrated that SDS exhibited the strongest binding affinity to the Aβ dimer, followed by CTAC and OG, with electrostatic forces playing a pivotal role. These outcomes align with experimental data, suggesting that SDS and CTAC, at concentrations above the CMC, diminish Aβ peptide aggregation and toxicity, whereas OG marginally increases toxicity.