Aggregation of Amyloid-like Peptides in Different Solvents.
Aggregation of Amyloid-like Peptides in Different Solvents.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Bangkok, TH · Author affiliation
Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.Location evidence
JE · Author affiliation · country only
Department of Physics, New Jersey Institute of Technology, Newark, New Jersey 07102-1982, United States.Location evidence
US · Author affiliation · country only
Department of Physics, New Jersey Institute of Technology, Newark, New Jersey 07102-1982, United States.Location evidence
Nagoya, JP · Author affiliation
Department of Complex Systems Science, Graduate School of Informatics, Nagoya University, Nagoya 464-8601, Japan.Location evidence
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Original abstract
The aggregation of amphipathic peptides into β-sheet rich structures is a hallmark of several neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. At the molecular level, the toxic mechanism of these peptides involves an increase in the permeation of the cellular membrane, which starts with the partition of nonpolar and polar residues at the water-lipid interface that facilitates aggregation. Here, we study this process using all-atom molecular dynamics simulations in four model peptides composed of 4 phenylalanine (F), 2 lysine (K), and 2 glutamic acid (E) under three solvent conditions. In two sequences, nonpolar and charged amino acids alternate along the chain (FKFEFKFE and FFKKFFEE), and, in the other two sequences (FFFKFEKE and FFFFKKEE), they are segregated to the N- and C-terminals. Peptides are solvated in water and octane to study aggregation in hydrophilic and hydrophobic solvents, respectively. In all simulations, peptides aggregate promptly, adopting mostly random coil conformations; except for FKFEFKFE, which spontaneously forms β-sheet conformations in water that resemble the cross-beta structures found in amyloid diseases. Aggregation takes place with a lower free energy of dimerization in octane compared to water. Simulations are also performed in a water-octane to mimic the water-lipid interface where amyloid peptides aggregate before damaging cell membranes. All peptides are spontaneously attracted to this polar-nonpolar interface which corresponds to a minimum in the free energy profile. At the interface, peptides generally exhibit low backbone interaction energies with a high content of secondary structure. The types of secondary structure formed in the system depend on the sequence pattern. In addition, the arrangement of polar and nonpolar residues modulates the free energy profile of peptide transfer from water to octane, and monomers adsorb at the interface more preferentially than the β-sheet dimer. These findings provide insights into how sequence pattern and solvent environment influence peptide aggregation, secondary structure formation, and interfacial behavior.