Figure presents representative snapshots from the resulting ensemble of fibril structures for the three polymorphs from these simulations. All three polymorphs are composed of extended β-strands that assemble into sheets. The strands for amylin 20 while those of polymorph 2 and Aβ 25-35 form parallel βsheet structures. For amylin 20-29 polymorph 1, hydrophobic contacts occur between the side chains of Phe, Ala, and Ile residues within the same β-sheet, while the side chains of Leu, Ala, and Ile form hydrophobic zippers between βsheets (Figure ). In contrast, the side chains of Phe, Ala, Ile, and Leu residues are aligned down the length of the β-sheets for polymorph 2, forming a string of hydrophobic interactions (and π-stacking interactions for Phe) between their neigboring residues, while the side chains of Ile, Leu, and Ala residues from opposite β-sheets additionally form hydrophobic zippers, similar to polymorph 1 (Figure and). For Aβ 25-35 , hydrophobic interactions occur between the side chains of Ala an Ile residues within the same β-sheet, as well as Leu and Ile residues from opposite β-sheets (Figure ). In addition, hydrogen bonding interactions are observed between Ser, Asn, and Lys residues between neighboring β-strands (Figure ). All three polymorphs obtained from the MD simulation exhibit structural features that are reasonable for amyloid fibrils. The average inter-sheet distances for the three structures are between 9.4 -10.4Å, and the average inter-strand spacings are between 4.9 -5.1Å (Table ). These values are in good agreement with the equatorial and meridional spacings observed in experimental fiber diffraction data of amyloid fibrils. Similarly, no unrealistic bond angle distortions or steric clashes are observed, and the (ψ, φ, ω) Ramachandran angles are all within allowed values (Table -S6).