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Molecular dynamics simulation on the inhibition mechanism of peptide‐based inhibitor of islet amyloid polypeptide ( IAPP ) to islet amyloid polypeptide ( IAPP 22–28 ) oligomers
Author(s) -
Zhou Shuangyan,
Wang Qianqian,
Ren Mengdan,
Zhang Ai,
Liu Huanxiang,
Yao Xiaojun
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12924
Subject(s) - oligomer , chemistry , peptide , amyloid (mycology) , islet , molecular dynamics , monomer , hydrogen bond , amylin , biochemistry , biophysics , insulin , biology , molecule , organic chemistry , inorganic chemistry , computational chemistry , endocrinology , polymer
Aggregation of islet amyloid polypeptide ( IAPP ) is implicated in the development of type 2 diabetes. The modified NFGAIL with double N ‐methylated at Gly24 and Ile26 has the property of soluble, non‐amyloidogenic, non‐cytotoxic, and the ability of inhibiting amyloid formation and cytotoxicity of IAPP . To discover the inhibition mechanism of this peptide inhibitor and provide useful information to design more potential peptide inhibitors, molecular dynamics simulations in explicit solvent were performed. The simulation results reveal that Gly24 and Ile26 are of importance in IAPP aggregation, and N‐methylation at these two key residues will disrupt the stability of formed oligomer and prevent the conformation transition of free monomer near the oligomer template. The origin of the N‐methylated peptide inhibitor inhibiting IAPP aggregation is that it can keep good binding with IAPP template by stable hydrogen bonding interaction. Furthermore, it cannot induce the conformational transition of free monomer by preventing the hydrogen bond interaction between free monomer and boundary peptide. The structural environment can largely affect the stacking of free monomers to the template. Our study sheds light on the inhibition mechanism of peptide inhibitor at molecular level and may provide guidance for the future design and discovery of new peptide inhibitors.