Robust Denaturation of Villin Headpiece by MoS2 Nanosheet: Potential Molecular Origin of the Nanotoxicity

Abstract

MoS2 nanosheet, a new two-dimensional transition metal dichalcogenides nanomaterial, has attracted significant attentions lately due to many potential promising biomedical applications. Meanwhile, there is also a growing concern on its biocompatibility, with little known on its interactions with various biomolecules such as proteins. In this study, we use all-atom molecular dynamics simulations to investigate the interaction of a MoS2 nanosheet with Villin Headpiece (HP35), a model protein widely used in protein folding studies. We find that MoS2 exhibits robust denaturing capability to HP35, with its secondary structures severely destroyed within hundreds of nanosecond simulations. Both aromatic and basic residues are critical for the protein anchoring onto MoS2 surface, which then triggers the successive protein unfolding process. The main driving force behind the adsorption process is the dispersion interaction between protein and MoS2 monolayer. Moreover, water molecules at the interface between some key hydrophobic residues (e.g. Trp-64) and MoS2 surface also help to accelerate the process driven by nanoscale drying, which provides a strong hydrophobic force. These findings might have shed new light on the potential nanotoxicity of MoS2 to proteins with atomic details, which should be helpful in guiding future biomedical applications of MoS2 with its nanotoxicity mitigated.

Mild Binding of Protein to C2N Monolayer Reveals Its Suitable Biocompatibility

“…Here, Q( t ) is defined as the ratio of the total number of native contacts, using a distance cutoff of 0.5 nm, with respect to the crystal structure at time t . Here, only residue pairs apart by at least three consecutive residues from each other were considered as defined in our previous study . The mean Q value averaged over six trajectories is shown in Figure A.…”

“…The native structure of HP35 contains a globular bundle of three α‐helices with an estimated folding time of 4.3 ± 0.6 µs at room temperature. Because of its fast folding kinetics, HP35 has been adopted to explore the biological effects of the graphene and MoS 2 materials. In our simulation, the HP35 was initially placed at a distance of 1.0 nm from the C 2 N monolayer (Figure A,B).…”

“…On the other hand, Chae and co‐workers found that MoS 2 (and WS 2 ) have limited cytotoxicity with no significant deleterious effect to cellular viability or genetic defects . Our previous theoretical studies have revealed that pristine MoS 2 can induce severe distortions in the structure of proteins due to its strong attraction, which causes the loss of tertiary structure and native protein function . Meanwhile, surface functionalization is often adopted to enhance biocompatibility.…”

Destabilization of amyloid fibrils on interaction with MoS2-based nanomaterials

“…The charges for these atoms were 0.76 and À0.38 in electronic units, respectively, and were based on electronic structure theory calculations. 53,54 As can be seen, the Mo potential is very attractive which will inuence the melting and transition temperature of the MoS 2 crystal or the hybrid system formed with the MoS 2 nanomaterials. For describing the interaction of amyloid bril, we employed the amber99sb-ildn force eld.…”

“…51,52 Previous computational studies have shown that molybdenum disulphide nanotubes and nanosurfaces can induce changes in the structure of helical and beta sheet peptides. 53,54 However, understanding of the interactions of the brils with molybdenum disulphide based materials is still elusive and calls for further theoretical scrutiny. In this study, the interaction of amyloid brils with molybdenum nanotubes and nanosurfaces was investigated using classical molecular dynamics simulations.…”