Theoretical Studies On Amino Modification Of DNA And Nanopore Sequencing By Two-Dimensional Materials

We mainly studied amino modification of DNA and DNA sequencing by two-dimensional?2D? nanopore materials in this thesis.In the first part,based on density functional theory and non-equilibrium Green's function method,the effect of adenine amino modification on DNA conductivity was researched.In the second part,DNA sequencing and DNA methylation recognition based on two-dimensional materials nanopore was studied.The primary research contents can be summarized as follows:In the first part of this thesis,the effects of amino modification on DNA conductivity were thoroughly studied.DNA becomes a candidate material for building molecular devices because of its self-recognition,self-assembly and other excellent characteristics.However,direct applications of natural DNA to molecular devices may still have some limitations,thus the modification of DNA is of great significance.The effect of C2 amino modification for adenine?the base formed is diaminopurine,abbreviated as D?on the geometric properties,electronic properties and charge transport properties of DNA was researched in detail.First,comparing the geometries before and after modification,it was found that a new hydrogen bonds is formed between amino modified base pairs DT?diaminopurine and thymine base pair? compared with the natural base pair AT,while the stability of DNA structure is maintained.Then,electronic properties of the systems were analyzed.The results show that the energy gap and the ionization energy of amino modified system are greatly reduced.The red-shift phenomena appear in the ultraviolet absorption spectra,and some charge transfer transitions increase.More importantly,we compared and analyzed electron transport properties along hydrogen bond direction between base pairs and along DNA chain direction before and after the modification.The electrical data measured by experiments show that the amino modification can enhance the conductivity of DNA.The innovation of this part is that the intrinsic mechanism of amino modification enhancing DNA conductivity is revealed.The HOMO level of amino modified DT base pair is closer to the HOMO level of GC?the base pair formed by guanine?G?-cytosine?C?? than that of natural AT,thus reducing the barrier of hole transition.This work would provide some theoretical guidance for the design of DNA-based molecular devices.The second part of the thesis focuses on DNA sequencing using two-dimensional with materials nanopore,especially the recognition of DNA methylation.The applied 2D materials include molybdenum disulfide and hexagonal boron nitride.DNA sequencing has important biological and physical significance.So far,it is generally believed that DNA sequencing technology has experienced three generations of development.Compared with traditional sequencing methods,2D nanopore sequencing has the advantages of high speed,high accuracy and low cost.In recent years,the emergence of two-dimensional materials such as graphene,molybdenum disulfide and hexagonal boron nitride provides a new application prospect for nanopore DNA sequencing.In addition to the sequencing for normal bases,accurate recognition of DNA methylaiton,especially cytosine methylation?mainly 5mC?is of great significance for early detection of some cancers.Molecular dynamics?MD? was carried out to simulate the processes of five different single-stranded DNA?composed by four natural bases and 5mC? passing through MoS₂ nanopore under electric field.The migration behavior of different single-strand DNA through MoS₂ nanopore,the average ion current and the normal distribution of ion current were compared under 4V bias.The results show that 5mC could be distinguished from cytosine?C? by the designed nanopore setup,while the differences between 5mC and other three natural bases are not obvious.We also compared the migration process of single stranded DNA composed by 5mC and C under 3 V bias.The results indicate that the recognition of 5mC from C bases could also be achieved under 3 V bias.The recognition of base 5mC and C can be realized at 3V bias or 4V bias.By comparing the average ion currents of 5mC and C,it is found that the discrimination effect between 5mC and C bases under 3V bias is better than that under 4V bias.In the second part,we also studied DNA sequencing by hexagonal boron nitride?hBN? nanopore.MD was used to simulate the process of two different single-stranded DNAs?basic units are C and 5mC? passing through hBN nanopore under electric field.The results show that 5mC and C can be identified by average ion current when passing through hBN nanopore under 4V bias.In other words,the recognition of methylation can be realized.