Computational analysis of hydrogen bonds network dynamics in the water layers surrounding Aβ(1-42) and Aβ(1-40) peptide dimers

• Published in: Journal of molecular liquids 2024-08, Vol.408, p.125342, Article 125342
• Main Authors: Zahraee, Hamed, Khoshbin, Zahra, Shahriar Arab, Seyed, Reza Bozorgmehr, Mohammad
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid-β; Autocorrelation function; Heterogeneity; Hydrogen bond
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2024.125342

[Display omitted] •Dimer heterogeneity effects on water hydrogen bond network were investigated.•The behavior of heterogeneous dimers was very similar to that of the Aβ42-42 dimers.•Water molecules in hydrogen bonds were more abundant around Aβ42 than Aβ40 monomers.•DMSO altered the distribution of hydrogen bonds around water molecules. The amyloid-β peptide (Aβ) dimer is involved in the development of Alzheimer’s disease through forming amyloid plaques. Aβ(1-40) and Aβ(1-42) are the most common and poisonous species causing Alzheimer’s disease. They form homogeneous dimers containing two similar peptides and heterogeneous dimers containing different ones. The low molecular weight, fast dynamics, and varying compositions of these dimers make it difficult to study them by conventional experimental methods. Hence, we clarify the effect of the diversity of the Aβ dimers on the structure of the water molecules around the peptides by the molecular dynamics (MD) simulation method in this study. MD simulations of the Aβ(1-40) and Aβ(1-42) monomers are also performed for the comparison. The calculations are repeated in the presence of dimethyl sulfoxide (DMSO). The water molecules positioned at distances of 0.5, 0.75, 1, 1.25, and 1.5 nm from the protein were chosen to investigate the distribution and dynamics of hydrogen bonds in the layers surrounding the peptide. The results show that the heterogeneity of the dimer system increases the percentage of hydrogen (H) atoms not involved in any water-water hydrogen bonds around the peptides in the different layers. While it decreases the percentage of H atoms involved in one and two water-water hydrogen bonds. The DMSO presence reduces the percentage of H atoms involved in two hydrogen bonds in the systems containing a mixture of water and DMSO. The average interaction energy of the dimers demonstrates the enhanced interactions of the two peptides in water in comparison with that in the mixture of water and DMSO. The behavior of the water molecules around the heterogeneous dimer is very similar to that around the Aβ(1-42) homogeneous dimer.