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- W2752676254 abstract "Human islet amyloid polypeptide (hIAPP) is a natively unfolded polypeptide hormone of glucose metabolism, which is co-secreted with insulin by the β-cells of the pancreas. In patients with type 2 diabetes, IAPP forms amyloid fibrils because of diabetes-associated β-cells dysfunction and increasing fibrillation, in turn, lead to failure of secretory function of β-cells. This provides a target for the discovery of small organic molecules against protein aggregation diseases. However, the binding mechanism of these molecules with monomers, oligomers and fibrils to inhibit fibrillation is still an open question. In this work, ligand and structure-based in silico approaches were used to identify novel fibrillation inhibitors and/or fibril binding compounds. The best pharmacophore model was used as a 3D search query for virtual screening of a compound database to identify novel molecules having the potential to be therapeutic agents against protein aggregation diseases. Docking and molecular dynamics simulation studies were used to explore the interaction pattern and mechanism of the identified novel small molecules with predicted hIAPP structure, its aggregation prone conformation and fibril forming segments. We show that catechins with galloyl group and molecules having two to three planar apolar rings bind to hIAPP structures and fibril forming segments with greater affinity. The differences in binding affinities of different compounds against several fibril forming segments of the peptide suggest that a mixture of active compounds may be required for treatment of aggregation diseases." @default.
- W2752676254 created "2017-09-15" @default.
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- W2752676254 creator A5064645858 @default.
- W2752676254 date "2017-10-01" @default.
- W2752676254 modified "2023-10-16" @default.
- W2752676254 title "Combined in silico approaches for the identification of novel inhibitors of human islet amyloid polypeptide (hIAPP) fibrillation" @default.
- W2752676254 cites W1580609715 @default.
- W2752676254 cites W1593001894 @default.
- W2752676254 cites W1869706611 @default.
- W2752676254 cites W1964172387 @default.
- W2752676254 cites W1968319881 @default.
- W2752676254 cites W1968431321 @default.
- W2752676254 cites W1971797738 @default.
- W2752676254 cites W1976851725 @default.
- W2752676254 cites W1980138515 @default.
- W2752676254 cites W1980240737 @default.
- W2752676254 cites W1981021420 @default.
- W2752676254 cites W1982653993 @default.
- W2752676254 cites W1985992988 @default.
- W2752676254 cites W1989810100 @default.
- W2752676254 cites W1991356605 @default.
- W2752676254 cites W1992192767 @default.
- W2752676254 cites W1995319721 @default.
- W2752676254 cites W1999909300 @default.
- W2752676254 cites W2000483769 @default.
- W2752676254 cites W2008708467 @default.
- W2752676254 cites W2009623261 @default.
- W2752676254 cites W2012108346 @default.
- W2752676254 cites W2016630460 @default.
- W2752676254 cites W2021388785 @default.
- W2752676254 cites W2023035838 @default.
- W2752676254 cites W2023954836 @default.
- W2752676254 cites W2026306293 @default.
- W2752676254 cites W2029582401 @default.
- W2752676254 cites W2033853317 @default.
- W2752676254 cites W2035687084 @default.
- W2752676254 cites W2036785665 @default.
- W2752676254 cites W2038392139 @default.
- W2752676254 cites W2039638928 @default.
- W2752676254 cites W2041037209 @default.
- W2752676254 cites W2043363703 @default.
- W2752676254 cites W2044172327 @default.
- W2752676254 cites W2045722951 @default.
- W2752676254 cites W2051027493 @default.
- W2752676254 cites W2056197009 @default.
- W2752676254 cites W2057709942 @default.
- W2752676254 cites W2058838921 @default.
- W2752676254 cites W2061111679 @default.
- W2752676254 cites W2063583344 @default.
- W2752676254 cites W2065232574 @default.
- W2752676254 cites W2067820229 @default.
- W2752676254 cites W2070815033 @default.
- W2752676254 cites W2074557858 @default.
- W2752676254 cites W2074726906 @default.
- W2752676254 cites W2076834744 @default.
- W2752676254 cites W2079932486 @default.
- W2752676254 cites W2082592680 @default.
- W2752676254 cites W2084317099 @default.
- W2752676254 cites W2085398335 @default.
- W2752676254 cites W2087357689 @default.
- W2752676254 cites W2091086263 @default.
- W2752676254 cites W2092625134 @default.
- W2752676254 cites W2097259690 @default.
- W2752676254 cites W2097691894 @default.
- W2752676254 cites W2100630099 @default.
- W2752676254 cites W2102993309 @default.
- W2752676254 cites W2105668062 @default.
- W2752676254 cites W2114367386 @default.
- W2752676254 cites W2114563838 @default.
- W2752676254 cites W2115168896 @default.
- W2752676254 cites W2121753059 @default.
- W2752676254 cites W2128460405 @default.
- W2752676254 cites W2128572087 @default.
- W2752676254 cites W2129507901 @default.
- W2752676254 cites W2130447483 @default.
- W2752676254 cites W2131107868 @default.
- W2752676254 cites W2134439639 @default.
- W2752676254 cites W2135706939 @default.
- W2752676254 cites W2135732933 @default.
- W2752676254 cites W2136989779 @default.
- W2752676254 cites W2156328030 @default.
- W2752676254 cites W2158698691 @default.
- W2752676254 cites W2161427213 @default.
- W2752676254 cites W2164187654 @default.
- W2752676254 cites W2171268876 @default.
- W2752676254 cites W2177317049 @default.
- W2752676254 cites W2336883206 @default.
- W2752676254 cites W2472005760 @default.
- W2752676254 doi "https://doi.org/10.1016/j.jmgm.2017.09.004" @default.
- W2752676254 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28917147" @default.
- W2752676254 hasPublicationYear "2017" @default.
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