Robust Denaturation of Villin Headpiece by MoS(2) Nanosheet: Potential Molecular Origin of the Nanotoxicity

MoS(2) 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 MoS(2) nanosheet with Villin Headpiece (HP35), a model protein widely used in protein folding studies. We find that MoS(2) 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 MoS(2) surface, which then triggers the successive protein unfolding process. The main driving force behind the adsorption process is the dispersion interaction between protein and MoS(2) monolayer. Moreover, water molecules at the interface between some key hydrophobic residues (e.g. Trp-64) and MoS(2) 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 MoS(2) to proteins with atomic details, which should be helpful in guiding future biomedical applications of MoS(2) with its nanotoxicity mitigated.