SUPR
Modeling of interactions between amyloid fibrils and disaccharides
Dnr:

NAISS 2024/5-434

Type:

NAISS Medium Compute

Principal Investigator:

Jan Swenson

Affiliation:

Chalmers tekniska högskola

Start Date:

2024-09-26

End Date:

2025-04-01

Primary Classification:

10603: Biophysics

Secondary Classification:

10304: Condensed Matter Physics

Tertiary Classification:

10399: Other Physics Topics

Allocation

Abstract

Recently, we have performed neutron diffraction experiments on lysozyme in aqueous solutions of the disaccharides trehalose and sucrose, using the diffractometer NIMROD at ISIS neutron scattering facility in UK. The measurements were carried out at the two pH values 2.0 and 3.5, where lysozyme denaturate and form amyloid fibrils at the lower pH, although to a much lower extent when the disaccharides were added to the solutions. However, it is challenging to analyze and modeling the experimental data and therefore we are using the newly developed software package Dissolve (Youngs, T. Molecular Physics, 2019, 117(22), p. 3464-3477) to create structural models of the investigated systems, which are in quantitative agreement with the diffraction data. To produce structural models of the fibrils and how the different solvent molecules interact with them we need to create models containing around 100 000 atoms. Therefore, the simulations become very time consuming and we need the super computers provided by NAISS to obtain structural models in a reasonable time. The project is of importance to understand how trehalose and sucrose can be used to reduce detrimental structural aggregation of lysozyme and the formation of amyloid fibrils, which is known to cause many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntington.