Overcoming the challenges of peptide simulations

A new paper marks a step forward in our understanding of peptide fragments and methods for simulating them.

Researchers from the Astbury Centre for Structural Molecular Biology and School of Chemistry have, for the first time, calculated the solubility diagram of amyloid β (16-22) peptide – a peptide fragment related to the onset of Alzheimer's disease. Their study sheds new light on how the solubility of various peptide aggregates depends on experimental conditions.

This is a significant objective given that self-assembled peptide aggregates play a key role in the onset of diseases such as Alzheimer’s and Parkinson's. Understanding the solubility of peptide aggregates is also crucial in biomaterials research as they can be useful, for example, as scaffolds for tissue engineering applications.

In a new paper, published in Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers present calculations of a solubility diagram of various aggregates formed by a fragment of the amyloid β peptide using a realistic protein model. These calculations have been verified experimentally.  

It has traditionally been challenging to create accurate thermodynamic phase diagrams for peptides, due to the computational resources required. Such diagrams describe the behaviour of molecules and materials at different concentrations and temperatures, giving insight into how they can be encouraged or prevented from forming under different conditions.

This paper, Thermodynamic phase diagram of amyloid β (16-22) peptide, demonstrates that a realistic model to represent the peptide, in combination with advanced computational techniques, can be used to simulate an equilibrium concentration and temperature phase diagram for the short amyloid β peptide.

A quantitative calculation of a phase diagram for peptides using a realistic protein model has never been presented before, and has never been validated with direct solubility measurements.

While the paper focuses on a particular example, it represents a highly encouraging step forward for the use of such models in the future. A better understanding of peptide assembly, which in general lack phase diagrams, could enhance our understanding to inform the development of treatments for amyloid diseases, and open up new possibilities in bioengineering.

The research was made possible through the award of a Cheney Fellowship to Professor Carol K. Hall, which allowed the development of a broad collaboration with members of the Astbury Centre for Structural Molecular Biology on peptide/protein aggregation.

Further reading

“Thermodynamic phase diagram of amyloid-β (16–22) peptide”, Proceedings of the National Academy of Sciences of the United States, Yiming Wang, Samuel J. Bunce, Sheena E. Radford, Andrew J. Wilson, Stefan Auer, and Carol K. Hall