Alzheimer’s disease (AD) is characterized by the presence of Amyloid-beta (Aβ) peptide, which has the propensity to fold into β-sheets under stress forming aggregated amyloid plaques. Nowadays many studies have focused on the development of novel, specific therapeutic strategies to slow down Aβ aggregation or control preformed aggregates. Albumin, the most abundant protein in the cerebrospinal fluid, was reported to bind Aβ impeding its aggregation. Recently, it has been reported that C-terminal (CTerm) of Human Albumin binds with Aβ1-42, impairs Aβ aggregation and promotes disassembly of Aβ aggregates protecting neurons. In this computational study, we have investigated the effect of CTerm on the conformational dynamics and the aggregation propensity of Aβ1-42 peptide. We have performed molecular dynamics simulations on the Aβ1-42-Aβ1-42 homodimer and Aβ1-42-CTerm of albumin heterodimer using the AMBER force field ff99SBildn. From the Potential of mean force (PMF) study and Binding free energy (BFE) analysis, we observed the association of Aβ1-42 peptide monomer with itself in the form of homodimer to be stronger than its association with the CTerm in the heterodimer complex. The difference in the number of residues in the Aβ1-42 peptide monomer (42 AAs) and CTerm (35 AAs) may be probable reason for the difference in association between the monomeric units in corresponding homodimer and heterodimer complexes. But even then CTerm shows a significant effect on the dimerization of Aβ1-42 peptide. Our findings therefore suggest that CTerm can be used for the disassembly of Aβ1-42 peptide monomer.
The Activating Effect of Strong Acid for Pd-Catalyzed Directed C–H Activation by Concerted Metalation-Deprotonation Mechanism