![Author ORCID: We display the ORCID iD icon alongside authors names on our website to acknowledge that the ORCiD has been authenticated when entered by the user. To view the users ORCiD record click the icon. [opens in a new tab]](https://chemrxiv.org/engage/assets/public/chemrxiv/images/logos/orcid.png)
Abstract
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 a↵ect 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.
