Effect of Surface Chemistry on Islet Amyloid Polypeptide Conformation

The formation of dense, linear protein arrays (fibrils) is the hallmark of a number of degenerativediseases, such as Alzheimer’s and type-2 diabetes. Protein fibrils have also attracted interestas building blocks for new materials. It has long been recognised that surfaces can affect thefibrillation 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, therate of fibril formation is lower than on other surfaces. To understand this, replica exchangemolecular dynamics simulations were used to investigate the conformations that hIAPP adopts onsurfaces of di↵erent hydrophobicity. The hydrophobic surface stabilizes ↵-helical structures, whichare quite di↵erent to those found on the hydrophilic surface and in bulk solution. There is alsoa greatly reduced conformational ensemble on the hydrophobic surface, due to long-lived contactsbetween hydrophobic residues on the protein and the surface. This new microscopic informationwill help us determine the mechanism of the enhancement of fibril formation on surfaces.