Silver nanoparticles alter the dimerization of Aβ42 studied by REMD simulations

Abstract

The aggregation of amyloid beta (Aβ) peptides is associated with the development of Alzheimer's disease (AD). However, there has been a growing belief that the oligomerization of Aβ species in different environments has a neurotoxic effect on the patient's brain, causing damage. It is necessary to comprehend the compositions of Aβ oligomers in order to develop medications that may effectively inhibit these neurotoxic forms that affect the nervous system of AD patients. Thus, dissociation or inhibition of Aβ aggregation may be able to prevent AD. To date, the search for traditional agents and biomolecules has largely been unsuccessful. In this context, nanoparticles have emerged as potential candidates to directly inhibit the formation of Aβ oligomers. The oligomerization of the dimeric Aβ peptides with or without the influence of a silver nanoparticle was thus investigated using temperature replica-exchange molecular dynamics (REMD) simulations. The physical insights into the dimeric Aβ oligomerization were clarified by analyzing intermolecular contact maps, the free energy landscape of the dimeric oligomer, secondary structure terms, etc. The difference in obtained metrics between Aβ with or without a silver nanoparticle provides a picture of the influence of silver nanoparticles on the oligomerization process. The underlying mechanisms that are involved in altering Aβ oligomerization will be discussed. The obtained results may play an important role in searching for Aβ inhibitor pathways.