Aspects of structural landscape of human islet amyloid polypeptide
- School of Physics, Beijing Institute of Technology, Beijing 100081 (China)
- Institute of Biopharmaceutical Research, Yangtze River Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd, Beijing 102206 (China)
- Department of Physics and Astronomy, Uppsala University, P.O. Box 803, S-75108 Uppsala (Sweden)
The human islet amyloid polypeptide (hIAPP) co-operates with insulin to maintain glycemic balance. It also constitutes the amyloid plaques that aggregate in the pancreas of type-II diabetic patients. We have performed extensive in silico investigations to analyse the structural landscape of monomeric hIAPP, which is presumed to be intrinsically disordered. For this, we construct from first principles a highly predictive energy function that describes a monomeric hIAPP observed in a nuclear magnetic resonance experiment, as a local energy minimum. We subject our theoretical model of hIAPP to repeated heating and cooling simulations, back and forth between a high temperature regime where the conformation resembles a random walker and a low temperature limit where no thermal motions prevail. We find that the final low temperature conformations display a high level of degeneracy, in a manner which is fully in line with the presumed intrinsically disordered character of hIAPP. In particular, we identify an isolated family of α-helical conformations that might cause the transition to amyloidosis, by nucleation.
- OSTI ID:
- 22416060
- Journal Information:
- Journal of Chemical Physics, Vol. 142, Issue 4; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); ISSN 0021-9606
- Country of Publication:
- United States
- Language:
- English
Similar Records
Fibrillar dimer formation of islet amyloid polypeptides
Early-stage human islet amyloid polypeptide aggregation: Mechanisms behind dimer formation