Hydrodynamic effects on β-amyloid (16-22) peptide aggregation.

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Computer simulations are crucial for studying amyloid aggregation.
• Implicit solvent models neglect solvent-induced correlations, affecting aggregation kinetics.
• Amyloid peptides like Aβ16-22 are implicated in neurodegenerative diseases.

Purpose of the Study:

• To investigate the effect of hydrodynamic interactions (HIs) on amyloid Aβ16-22 peptide aggregation.
• To explore the aggregation pathways and resulting structures using a multi-scale simulation technique.
• To bridge the gap between simplified simulations and experimental observations.

Main Methods:

• Application of the multi-scale Lattice Boltzmann Molecular Dynamics (LBMD) technique.
• Utilizing the OPEP coarse-grained force field for peptide representation.
• Parameter tuning to match experimental diffusivity of species.

Main Results:

• Hydrodynamic interactions (HIs) were shown to impact aggregation kinetics and oligomer size fluctuations.
• HIs favor fusion and exchange dynamics between aggregates, guiding the growth of the largest cluster.
• Simulations revealed the transition from ellipsoidal assemblies to elongated, twisted aggregates (100 peptides) and novel branched fibril-like structures (1000 peptides).

Conclusions:

• LBMD simulations including HIs provide a more accurate representation of amyloid aggregation.
• The study demonstrates the critical role of solvent effects in determining fibril morphology and aggregation dynamics.
• The findings offer insights into the formation of experimentally observed amyloid structures, including disordered fibril-like forms.