Critical roles of key domains in complete adsorption of Aβ peptide on single-walled carbon nanotubes: insights with point mutations and MD simulations

Abstract

Owing to the influence of nanomaterials on biomacromolecular behavior, their potential applications are rapidly gaining attention. Based on atomistic molecular dynamics simulation studies we have recently reported that the full-length Aβ peptide, whose self-assembly is associated with Alzheimer's disease, adsorbs rapidly on single-walled carbon nanotubes, thereby losing its natural propensity to collapse. Here, we investigate the mechanistic overlap between the peptide's compactification and its adsorption, while decoupling the roles of hydrophobicity and aromaticity via point mutations. The collapse mechanism is correlated with interactions between the central hydrophobic core (HP1) and the peptide's C-terminal domain, which are almost exactly compensated by interactions arising from the nanotube after complete adsorption. Adsorption is initiated by HP1 and consolidated by strong interactions arising from the N-terminal domain. Altering the hydrophobicity, but not the aromatic character, of the central residue in HP1 decreases the collapse probability. On the other hand, the adsorption propensity is dramatically reduced when either the hydrophobicity or the aromatic character in HP1 is compromised. The hydrophobicity of HP1 is responsible for dewetting transitions that facilitate its initial interactions with the nanotube, which then lead to very favorable interactions with the nanotube.

Aβ self-association and adsorption on a hydrophobic nanosurface: competitive effects and the detection of small oligomers via electrical response

“…23,24 However, structural information on the monomeric and various self-assembled forms has been obtained via NMR methods. [35][36][37][38][39] Kim and Lee rst showed that 1,2-(dimethoxylmethano) fullerene specically binds to the KLVFF region of the Ab protein, thereby suppressing Ab aggregation. 7,18,[26][27][28][29][30] Non-covalent interactions arising from various nanomaterials could be harnessed for modulating the intrinsic selfassembly characteristics of Ab.…”

Influence of Au nanoparticles on the aggregation of amyloid-β-(25–35) peptides

“…The utilization of nanoparticles for the treatment of proteinaggregation diseases is an important one among these applications. [23][24][25][26] But researches on the interaction between Au NPs and Ab proteins have not been reported yet, due to the computationally huge simulations required to simulate all the NP atoms, especially for large NPs. [10][11][12][13][14][15][16][17][18][19][20][21][22] By now, the phenomena of the inuence of Au NPs on the Ab protein aggregations has already been reported using various techniques such as scanning electron microscopy, transmission electron microscopy, atom force microscopy and optical spectroscopies.…”

Perturbations in inter-domain associations may trigger the onset of pathogenic transformations in PrPC: insights from atomistic simulations

“…13,[52][53][54][55][56][57] In this study, using fully atomistic molecular dynamics (MD) simulations, we have studied the conformational and dynamical implications of a minor perturbation of H1 interactions, namely the loss of a single side chain-side chain hydrogen bond Y149-D202, that links H1 with the rest of the globular domain of PrP C . 13,[52][53][54][55][56][57] In this study, using fully atomistic molecular dynamics (MD) simulations, we have studied the conformational and dynamical implications of a minor perturbation of H1 interactions, namely the loss of a single side chain-side chain hydrogen bond Y149-D202, that links H1 with the rest of the globular domain of PrP C .…”