Effect of caffeine on the aggregation of amyloid-β-A 3D RISM study.

J Chem Phys

Department of Chemistry, University of Delhi, Delhi 110007, India.

Published: March 2024

Alzheimer's disease is a detrimental neurological disorder caused by the formation of amyloid fibrils due to the aggregation of amyloid-β peptide. The primary therapeutic approaches for treating Alzheimer's disease are targeted to prevent this amyloid fibril formation using potential inhibitor molecules. The discovery of such inhibitor molecules poses a formidable challenge to the design of anti-amyloid drugs. This study investigates the effect of caffeine on dimer formation of the full-length amyloid-β using a combined approach of all-atom, explicit water molecular dynamics simulations and the three-dimensional reference interaction site model theory. The change in the hydration free energy of amyloid-β dimer, with and without the inhibitor molecules, is calculated with respect to the monomeric amyloid-β, where the hydration free energy is decomposed into energetic and entropic components, respectively. Dimerization is accompanied by a positive change in the partial molar volume. Dimer formation is spontaneous, which implies a decrease in the hydration free energy. However, a reverse trend is observed for the dimer with inhibitor molecules. It is observed that the negatively charged residues primarily contribute for the formation of the amyloid-β dimer. A residue-wise decomposition reveals that hydration/dehydration of the side-chain atoms of the charged amino acid residues primarily contribute to dimerization.

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0202636DOI Listing

Publication Analysis

Top Keywords

inhibitor molecules
16
hydration free
12
free energy
12
alzheimer's disease
8
dimer formation
8
amyloid-β dimer
8
dimer inhibitor
8
residues contribute
8
formation
5
amyloid-β
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!