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Updated: May 31, 2026
08:48
High-Resolution Neutron Spectroscopy to Study Picosecond-Nanosecond Dynamics of Proteins and Hydration Water
Published on: April 28, 2022
Role of water in protein aggregation and amyloid polymorphism
D Thirumalai1, Govardhan Reddy, John E Straub
1Biophysics Program, Institute for Physical Science and Technology, Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States. thirum@umd.edu
Accounts of Chemical Research
|July 19, 2011
Summary
Water significantly influences protein aggregation in neurodegenerative diseases. Understanding water
Area of Science:
- Biophysics
- Computational Chemistry
- Neuroscience
Background:
- Neurodegenerative diseases are linked to amyloid plaques formed from protein oligomers and fibrils.
- Current understanding of protein aggregation mechanisms, particularly in vivo, is incomplete.
- The role of solvent, specifically water, in protein aggregation has been largely overlooked in favor of protein-centric perspectives.
Purpose of the Study:
- To investigate the impact of water interactions on protein folding and aggregation.
- To elucidate the biophysical principles governing amyloid formation through computational simulations.
- To provide a structural and kinetic basis for understanding oligomer and fibril growth.
Main Methods:
- Explicit molecular dynamics simulations were employed.
- Simulations focused on amyloid beta (Aβ) monomers and fragments, and a yeast prion peptide.
- Analysis of water's role in monomer folding, oligomerization, and protofilament formation.
Main Results:
- Water expulsion is a critical barrier for forming aggregation-prone amyloid beta structures (N*).
- Hydrophobic sequences aggregate faster as water is expelled, forming disordered oligomers then ordered fibrils.
- Hydrophilic sequences can form water-stabilized metastable intermediates, slowing fibril growth.
Conclusions:
- Water plays a multifaceted role in protein aggregation, influencing both kinetics and structure.
- A two-step model, involving initial water expulsion and subsequent ordered assembly, is proposed for amyloid formation.
- Distinct polymorphic structures arise from different initial aggregation states influenced by water.
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