Molecular dynamics study of Abeta monomers and oligomers interacting with cofactors




Kim, Seogwon

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Amyloid-beta peptides are implicated in the Alzheimer's disease (AD), an age-related neurodegenerative disorder. In this work, we study the dynamics of Abeta monomer and oligomers in water and interacting with cofactors such as naproxen or lipid monolayer. All-atom force field combined with fast implicit solvent model and replica exchange molecular dynamics is used to obtain exhaustive sampling of Abeta monomer and oligomer conformations in water. Similar methodology is used to study the interaction of Abeta dimer and naproxen. The antiaggregation effect and the utility of naproxen as pharmaceutical agent against AD are discussed. In an attempt to understand the Abeta-membrane interaction which is believed to be responsible for cell toxicity, we study the interaction of Abeta monomer and lipid monolayer. A new force field for DMPC monolayer consistent with CHARMM19+SASA model is presented. A reliable statistical analysis of Abeta monomer bound to DMPC monolayer demonstrates that membrane interaction profoundly perturbs the structures of both the peptide and lipid monolayer.



Biophysics, Abeta peptides, Alzheimer's disease, Drug design, Implicit solvent, Lipid membrane, Molecular dynamics