Interaction Mechanism Between Silicene,MoS₂ And Protein Based On Molecular Dynamics Simulation

Nanomaterials are widely used in various fields because of their excellent physical and chemical properties.The ensuing consequence is that nanomaterials will inevitably enter the environment and then enter the human body by means of breathing,skin contact.In addition,the widespread application of nanomaterials in in vivo drug delivery and disease diagnosis also lead to the retention of nanomaterials in the human body.Exogenous nanomaterials interact with biological components such as proteins,nucleic acids and cell membranes in the body,thereby affecting the vital functions of the human body and exhibiting certain biological effects.Under these current situations,we urgently require to understand the action mechanism between nanomaterials and biomolecules,and have an in-depth understanding of the toxicity and biological effects of materials.In this paper,molecular dynamics simulation method is adopted to explore the interaction mechanism of 2D silicene,MoS₂ nanosheet and MoS₂ nanotube with several proteins,revealing the biological effects of these three materials.Chapter 1:An overview of nanomaterials,introduction of molecular dynamics simulation,silicene and molybdenum disulfide nanomaterials.Finally,the three research works of this paper were briefly described.Chapter 2:The interaction between silicene nanosheet and protein.Silicene,an emerging 2D nanomaterial with the puckered hexagonal structure,is expected to be a potential candidate for future applications in biomedical fields.It is important and urgent to study the biosafety of silicene.In this work,the molecular dynamics simulation was utilized to investigate the interaction between silicene monolayer and Villin Headpiece subdomain?HP35?.The results showed that,as a globular model protein extensively used in molecular simulations,HP35 could be rapidly attracted onto the surface of silicene and formed a stable binding mode without the significant change of contact area as well as orientation of protein.No significant structural distortion of HP35 was observed in the four simulations.Moreover,energy analysis showed that the residues Leu1,Asp3,Arg14,Ser15 and Phe35 played an important role in the adsorption process and the three hydrophobic residues Phe6,Phe10 and Phe17 that were important to maintain the HP35's structure did not interact closely with silicene,which further indicated the integrity and stability of protein.These results support that silicene has suitable biocompatibility to HP35.Chapter 3:The interaction between MoS₂ nanosheet containing vacancy defects and YAP65.The surface characteristics of nanomaterials affect their combination with biomolecules,and the inescapable defects on the surface of nanomaterials could alter materials structure and surface properties.In this work,three representative MoS₂ nanosheets with different vacancy defects were designed based on the structure and composition of the material.The interaction processes between the three materials and Yes-kinase associated domain protein?YAP65 WW domain?were investigated using molecular dynamics simulations.The results indicated that the third?-strand of YAP65 was lost in the binding to MoS₂,which is due to the favorable Van der Waals interaction between YAP65 and MoS₂.Compared with ideal MoS₂ sheet,the two defective MoS₂ sheet(D_9p-MoS₂,D_12n-MoS₂)significantly accelerated the destruction of the third?-strand of YAP65.This should be because defect makes the surface of MoS₂ activated and charged.On the surface of MoS₂with the vacancy defects of diverse size,YAP65 displayed similar structural damage,indicating that the size of defects has little effect on MoS₂ toxicity.These findings elucidate the effect of defects on the nanotoxicity of MoS₂.Chapter 4:The interaction between MoS₂ nanotube and signaling protein system.Herein,molecular dynamics simulations were performed to investigate the effect of MoS₂ nanotube on the binding process of the signaling protein YAP65,an important Yes kinase-associated protein domain?WW domain?,to the proline rich motif ligand?PRM?.Four systems were designed based on the different initial binding modes among WW domain,PRM and MoS₂ nanotube,and observed two ways to affect the binding of WW domain to PRM.The first pathway,the active site in WW domain was occupied by MoS₂ nanotube,which prevents WW domain from binding to PRM.In the second pathway,WW domain was bound to PRM with residues W17 and F29 instead of the two highly conserved residues?Y28 and W39?,forming an unstable combination.These two results might cause WW domain to lose its original function or to pass the mistaken signal.However,MoS₂ nanotube did not destroy the structure and binding of WW domain and PRM in the composite.These findings provide more valuable insights into the nanotoxicity of MoS₂ nanotube.