Characterisation of the structure and oligomerisation of islet amyloid polypeptides (IAPP): A review of molecular dynamics simulation studies
MetadataShow full item record
Human islet amyloid polypeptide (hIAPP) is a naturally occurring, intrinsically disordered protein whose abnormal aggregation into amyloid fibrils is a pathological feature in type 2 diabetes, and its cross-aggregation with amyloid beta has been linked to an increased risk of Alzheimer’s disease. The soluble, oligomeric forms of hIAPP are the most toxic to ß-cells in the pancreas. However, the structure of these oligomeric forms is difficult to characterise because of their intrinsic disorder and their tendency to rapidly aggregate into insoluble fibrils. Experimental studies of hIAPP have generally used non-physiological conditions to prevent aggregation, and they have been unable to describe its soluble monomeric and oligomeric structure at physiological conditions. Molecular dynamics (MD) simulations offer an alternative for the detailed characterisation of the monomeric structure of hIAPP and its aggregation in aqueous solution. This paper reviews the knowledge that has been gained by the use of MD simulations, and its relationship to experimental data for both hIAPP and rat IAPP. In particular, the influence of the choice of force field and water models, the choice of initial structure, and the configurational sampling method used, are discussed in detail. Characterisation of the solution structure of hIAPP and its mechanism of oligomerisation is important to understanding its cellular toxicity and its role in disease states, and may ultimately offer new opportunities for therapeutic interventions.
Showing items related by title, author, creator and subject.
FTIR studies of the similarities between pathology induced protein aggregation in vivo and chemically induced protein aggregation ex vivoTidy, R.; Lam, V.; Fimognari, N.; Mamo, John; Hackett, M. (2016)© 2016 Elsevier B.V.Fourier transform infrared (FTIR) spectroscopy has been well documented to discriminate between protein secondary structures, at the micron scale. This capability has enabled in situ localization of ...
Role of the cell membrane interface in modulating production and uptake of Alzheimer's beta amyloid proteinBharadwaj, Prashant; Solomon, T.; Malajczuk, C.; Mancera, Ricardo; Howard, M.; Arrigan, Damien; Newsholme, Philip; Martins, R. (2018)© 2018 Elsevier B.V. The beta amyloid protein (Aß) plays a central role in Alzheimer's disease (AD) pathogenesis and its interaction with cell membranes in known to promote mutually disruptive structural perturbations ...
Subaer (2004)Inorganic geopolymers or simply geopolymers based on silico-aluminate are relatively novel materials with a wide range of potential applications. The mAln purpose of the present study was to experimentally investigate the ...