Robust Denaturation of Villin Headpiece by MoS2 Nanosheet: Potential Molecular Origin of the Nanotoxicity.
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.
School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
Zonglin
Z
Gu
School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
Zaixing
Z
Yang
Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Seung-Gu
SG
Kang
Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Jerry R
JR
Yang
Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, 213001, China.
Judong
J
Luo
School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.|Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.|Department of Chemistry, Columbia University, New York, NY 10027, USA.
Ruhong
R
Zhou