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Methods of Ex Situ and In Situ Investigations of Structural Transformations: The Case of Crystallization of Metallic Glasses
Published on: June 7, 2018
Thermodynamic analysis of structural transitions during GNNQQNY aggregation
Kenneth L Osborne1, Michael Bachmann, Birgit Strodel
1Institute of Complex Systems: Structural Biochemistry, Research Centre Jülich, 52425 Jülich, Germany.
Proteins
|February 15, 2013
Summary
Amyloid protein aggregation, common in neurodegenerative diseases, can be studied using smaller protein domains. Simulations show GNNQQNY aggregation is driven by H-bonds, forming beta-sheets early in the process.
Area of Science:
- Biophysics
- Computational Biology
- Neuroscience
Background:
- Amyloid protein aggregation is a hallmark of neurodegenerative diseases like Alzheimer's.
- Similar aggregation pathways suggest studying smaller protein domains is sufficient for understanding amyloid formation.
Purpose of the Study:
- To investigate the thermodynamics of structural transitions during amyloid aggregation.
- To simulate the GNNQQNY prion domain of yeast Sup35 to understand its aggregation pathway.
Main Methods:
- Coarse-grained modeling for efficient simulation.
- Replica-exchange molecular dynamics to gather statistics at multiple temperatures.
- Analysis of thermodynamic quantities and orientational order parameters for GNNQQNY systems.
Main Results:
- Amyloid aggregation of the GNNQQNY sequence is primarily driven by hydrogen bond formation.
- Beta-sheet structures form early in the aggregation process.
- Condensation and ordering occur simultaneously, indicated by a single heat capacity peak.
Conclusions:
- Simulating smaller amyloid domains like GNNQQNY provides insights into the fundamental mechanisms of amyloid formation.
- Hydrogen bonding is a key driver for the aggregation of hydrophilic sequences.
- The simultaneous nature of aggregation and ordering suggests a coupled process in amyloid assembly.
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