Idealized Models of Protofilaments of Human Islet Amyloid Polypeptide

作者：Li Yiyu; Hatmal Ma'mon M; Langen Ralf; Haworth Ian S^*

来源：Journal of Chemical Information and Modeling, 2012, 52(11): 2983-2991.

DOI：10.1021/ci300300e

Fibrils formed by assembly of human islet amyloid polypeptide (hIAPP) are found in most patients with type II :diabetes: Structurally, these fibrils are,composed of multiple protofilaments and are characterized by extended beta sheets, variable helical twists, and different morphologies. We have previously derived models for the hIAPP protofilament using simulations constrained by data from EPR spectroscopy In the current work, these models were used as a basis for generating idealized hIAPP protofilaments with symmetrical geometrical properties using a new algorithm, MFIBRIL. We show good agreement. of the idealized protofilaments with experimental data for amino acid side chain: orientations and geometrical features including the inter-beta sheet distance and the protofilament radius. These idealized protofilaments can be used,in MFIBRIL to generate fibril Models that may be experimentally testable at the molecular level. MFIBRIL can also be used for building structures of any repetitive molecular assembly starting With a single building block obtained from any source.

• 出版日期2012-11