ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
iapp-surface-final with SI.pdf (5.83 MB)
0/0

Effect of Surface Chemistry on Islet Amyloid Polypeptide Conformation

preprint
revised on 11.08.2020 and posted on 12.08.2020 by David Cheung
The formation of dense, linear protein arrays (fibrils) is the hallmark of a number of degenerative
diseases, such as Alzheimer’s and type-2 diabetes. Protein fibrils have also attracted interest
as building blocks for new materials. It has long been recognised that surfaces can affect the
fibrillation process. Recent work on the model fibril forming protein human islet polypeptide
(hIAPP) has shown that while the protein concentration is highest at hydrophobic surfaces, the
rate of fibril formation is lower than on other surfaces. To understand this, replica exchange
molecular dynamics simulations were used to investigate the conformations that hIAPP adopts on
surfaces of di↵erent hydrophobicity. The hydrophobic surface stabilizes ↵-helical structures, which
are quite di↵erent to those found on the hydrophilic surface and in bulk solution. There is also
a greatly reduced conformational ensemble on the hydrophobic surface, due to long-lived contacts
between hydrophobic residues on the protein and the surface. This new microscopic information
will help us determine the mechanism of the enhancement of fibril formation on surfaces.

History

Email Address of Submitting Author

david.cheung@nuigalway.ie

Institution

NUI Galway

Country

Ireland

ORCID For Submitting Author

0000-0002-3994-2295

Declaration of Conflict of Interest

No conflict of interest

Exports

Logo branding

Exports