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Updated: Sep 13, 2025
08:04
Excitonic Hamiltonians for Calculating Optical Absorption Spectra and Optoelectronic Properties of Molecular Aggregates and Solids
Published on: May 27, 2020
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A Coarse-Grained MD Model for Disorder-To-Order Transitions in PolyQ Aggregation
Maurice Dekker1, Mark L van der Klok1, Erik Van der Giessen1
1Zernike Institute for Advanced Materials, University of Groningen, Groningen 9747 AG, The Netherlands.
Journal of Chemical Theory and Computation
|August 1, 2025
Summary
Polyglutamine (polyQ) aggregation in neurodegenerative diseases was modeled using molecular dynamics. Longer polyQ chains showed faster aggregation, revealing key mechanisms like beta-sheet elongation.
Area of Science:
- Biophysics
- Neuroscience
- Computational Biology
Background:
- Polyglutamine (polyQ) aggregation is implicated in neurodegenerative diseases like Huntington's disease.
- Understanding polyQ aggregation mechanisms is crucial for therapeutic development.
Purpose of the Study:
- To develop and validate a coarse-grained molecular dynamics model for polyQ aggregation.
- To explore diverse aggregation pathways and the impact of sequence length.
Main Methods:
- Coarse-grained molecular dynamics simulations calibrated with atomistic data and experiments.
- Systematic variation of interaction parameters to explore aggregation pathways.
- Seeded aggregation simulations to analyze growth mechanisms.
Main Results:
- Observed aggregation pathways ranging from nucleated growth to liquid-to-solid phase transitions.
- Amyloid growth primarily occurred via beta-sheet elongation, with steric zippering also noted.
- Longer polyQ sequences (Q48) aggregated significantly faster than shorter ones (Q23).
Conclusions:
- The developed model offers a versatile framework for studying polyQ aggregation.
- Chain length is a critical factor influencing polyQ aggregation kinetics.
- The model provides insights into broader aggregation mechanisms and sequence variations.
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