Molecular Dynamics Studies On The Interactions Between Novel Two-dimensional Nanomaterials And Biomolecules

The two-dimensional(2D)nanomaterials(NMs)and their related heterostructures with unique compositional,structural and physicochemical features,such as graphene and h-BN,have lately attracted significant attentions.There are growing concerns about the knowledge of interaction between 2D NMs and biomolecules,and the potential applications of 2D NMs in the fields of biomedicine and single-molecular sequencing.Therefore,a deeper understanding of the interactions between NMs and biomolecules can assist rational usage of NMs in biological applications.A variety of optical techniques,such as single-molecule fluorescence,super-resolution microscopy and optical tweezer,have been rendered as effective experimental tools to reveal single-molecular information of NMs and biomolecules.Complementary to experiments,Molecular dynamics(MD)simulations have also been widely adopted to illustrate the interactions of NMs with biomolecules.MD simulations can not only unveil mechanisms of the interaction,but also provide nanoscale dynamics which might not be observed in experiments.In this thesis,by employing MD simulation methods,we investigate the nanoscale beheviors of the interactions between NMs and biomolecules,such as protein confinement on 2D NMs,and DNA sieving effect of 2D NMs.Firstly,we investigate the impact of surface inhomogeneity of graphene oxide(GO)on the assembly of amyloid-beta A?16-21 peptides on GO surfaces with different degrees of oxidation using MD simulations.Abnormal peptide assembly and aggregation is associated with an array of neurodegenerative diseases including Alzheimer's disease(AD).A detailed understanding of how nanostructured materials such as oxidized graphene perturb the peptide assembly and subsequently induce fibril dissociation may open new directions for the development of potential AD treatments.We find that nonuniform GO nanosheets(in terms of oxidation sites)have a much stronger perturbation effect on the structure of A?16-21 assembly.The A? peptides exhibit a remarkable tendency in binding to the scattered interfaces between unoxidized and oxidized regions,which induces the dissociation of A? amyloid fibril.These findings should deepen our understanding of surface-induced peptide dissociation and stimulate discovery of alternative AD treatments.Next,using MD,we show that spontaneous protein stretching can be realized by a 2D heterostructure composed of a hexagonal boron nitride(h-BN)nanoribbon stitched with two graphene(GRA)sheets(i.e.,a sandwiched GRA/BN/GRA structure).Protein stretch and confinement in nanochannels is critical for advancing single-molecule detection techniques.Our work show that this planar nanochannel permits effective capture and elongation of three representative intrinsically disordered proteins including amyloid-?(1-42),polyglutamine(42)and ?-synuclein(61-95).Moreover,we found that the extremely narrow h-BN stripe can provide stronger confinement for longer polyglutamine chain after being stretched.Our approach has the potential to facilitate the bona fide readout of single-molecule protein sequencing techniques.Moreover,we study the ionic conduction oscillations in atomically thin sub-nanometer pores.As a supplement to the experimental work,our MD simulations further show that the ionic Coulomb blockade in atomically thin nanopores stems from single ion binding,whereas the ion translocation comes from the binary effect of multiple ions.Our work provides a deeper understanding of ionic Coulomb blockade effect under extreme confinements in atomically thin nanopores.At last,we demonstrate a 2D nanofluidic sieve consisting of an in-plane GRA/h-BN nanoarray,which enables ultra-high resolution in the successful separation of four types of single nucleotides.Regular nanofluidic sieving structures are emerging as rapid and compatible on-chip techniques for biomolecular separation,but it is still far away from a single-nucleotide resolution.In our MD simulations,the alternating GRA and h-BN stripes can create size-dependent energy barriers for adsorbed nucleotides,which provide a strong modulation for their mobility,thus causing distinct band separations on the 2D surface.We further show that this 2D sieve is particularly sensitive when the sample dimensions are within the range from a half period to one period of the nanoarrayOverall,by using MD simulations,the interactions between some 2D NMs and biomolecules,such as protein stretching and confinement in 2D heterostructures,and single-nucleotide separation in 2D arrays,are studied in this thesis.We hope these results can provide insights for deeper understanding of the interations between 2D NMs and biomolecules,and aid in the combination of optical techniques and 2D NMs in the applications of bionanotechnology.