Fatty acids compete with A? in binding to serum albumin by quenching its conformational flexibility (Biophysical Journal)

Human serum albumin (HSA) has been identified as an important regulator of A? fibrillization both in blood plasma and in cerebrospinal fluid. Fatty acids bind to HSA, and high serum levels of fatty acids increase the risk of Alzheimer`s disease. In vitro, fatty acid-loaded HSA (FA·HSA) loses the protective effect against A? fibrillization, but the mechanism underlying the interference of fatty acids on A?-HSA interactions has been unclear. Here we used molecular dynamics simulations to gain atomic-level insight on the weak binding of monomeric A?40 and A?42 peptides with apo and FA·HSA.