Influence of fullerenol on hIAPP aggregation: amyloid inhibition and mechanistic aspects

Abstract

C60(OH)24inhibits hIAPP aggregation by suppressing the fibril-prone structure and destabilizes hIAPP protofibrils by binding to the amyloid core region.

Pristine and Hydroxylated Fullerenes Prevent the Aggregation of Human Islet Amyloid Polypeptide and Display Different Inhibitory Mechanisms

“…Every hIAPP dimer was put in the center of a cubic box with a side length of 6.7 nm. Four C 60 or four C 60 (OH) 8 molecules were displaced in the solvated peptide system at random thus nanoparticle: peptide is 2:1 at molar ratio, which were consistent with previous simulation studies (Bai et al, 2019). The partial charges of oxygen and hydrogen atoms in hydroxyl groups were −0.8 and +0.3, and that of carbon atoms bonded with hydroxyl groups in C 60 (OH) 8 was +0.5, while other carbon atoms were uncharged (Goldsbury et al, 2000).…”

“…Both REMD and MD simulations are performed in the isothermal-isobaric (NPT) ensemble at a pressure of 1 bar using GROMACS−4.5.3 software package (Sugita and Okamoto, 1999;Nadler and Hansmann, 2008). We choose OPLS force field TIP4P water molecules, consistent with previous computational studies of hIAPP (Qi et al, 2014;Mo et al, 2016;Bai et al, 2019). hIAPP molecules are kept from the water box at least for 1.0 nm.…”

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

“…GQDs for in vivo mitigation of T2D amyloidosis.By combining all-atom REMD and MD simulations, AFM and TEM images, ThT and cell toxicity assays, Mo et al[957][958][959] examined the influences of hydroxylated carbon nanotubes and fullerenes on the fibrillization of hIAPP. REMD and MD simulations demonstrated that both CNT-OHs and C60OHs not only suppress the formation of β-sheet and β-hairpin-containing amyloidogenic precursor of hIAPP, but also remodel or disassemble preformed hIAPP protofibrils/fibrils.…”

“…Turbidity analyses, ThT fluorescence assays, CD microscopies, TEM and AFM images provide direct evidence for the simulation-predicted β-sheet inhibition and protofibril-disruption by hydroxylated CNTs/fullerenes. SH-SY5Y cell viability assays demonstrated the rescue effect of C60OHs on hIAPP-induced cytotoxicity.958 The REMD simulations by Bai et al958,959 showed that C60, C60(OH)8 and C60(OH)24 possess different inhibitory effects on the β-sheet formation of hIAPP: the β-sheet content of hIAPP dimer in the presence of C60, C60(OH)8 and C60(OH)24 is respectively 1.8, 4.2, and 5.6% (the β-sheet content of hIAPP dimer alone is 10.8%). These data reveal that hydroxylation extents modulate the inhibition capacity of C60OHs against hIAPP aggregation.…”

Recent development of atomistic force fields and simulations of intrinsically disordered proteins

“…越来越多的研究开始以IDPs作为药 物靶标, 并且已经发现了一些小分子能够结合IDPs [12] . 图 7 (a) hIAPP二聚体结合富勒醇前后的构象系综中聚类最大类的代表结构 [107] ; (b) Aβ42结合HT前后的构象系综 [108] ; (c) c-Myc 402-412 与10058-F4结合态的构象系综 [109] (网络版彩图) Figure 7 (a) The representative conformations for the first most-populated cluster of hIAPP dimer with or without C 60 (OH) 24 [107]; (b) the structural ensembles of Aβ42 with or without HT [108]; (c) the structural ensemble representing the bound state of c-Myc 402-412 and 10058-F4 [109] (color online).…”