Modeling Cu2+-Aβ complexes from computational approaches

Amyloid plaques formation and oxidative stress are two key events in the pathology of the Alzheimer disease (AD), in which metal cations have been shown to play an important role. In particular, the interaction of the redox active Cu2+ metal cation with Aβ has been found to interfere in amyloid aggregation and to lead to reactive oxygen species (ROS). A detailed knowledge of the electronic and molecular structure of Cu2+-Aβ complexes is thus important to get a better understanding of the role of these complexes in the development and progression of the AD disease. The computational treatment of these systems requires a combination of several available computational methodologies, because two fundamental aspects have to be addressed: the metal coordination sphere and the conformation adopted by the peptide upon copper binding. In this paper we review the main computational strategies used to deal with the Cu2+-Aβ coordination and build plausible Cu2+-Aβ models that will afterwards allow determining physicochemical properties of interest, such as their redox potential.