Theoretical Studies On DNA Sequencing And Methylation Detection Based On Adsorption Of Nucleobases On Two-dimensional Materials

DNA is composed of four natural bases(adenine,guanine,cytosine,and thymine,abbreviated as A,G,C,and T)in a certain sequence,which carries the important genetic information for life and its vital processes.Developing faster,cheaper,and more accurate methods for DNA sequencing have been a crucial research goal in many intersecting fields such as biology,physics,and chemistry.In recent years,the third-generation of DNA sequencing,which characterized by single-molecule recognition,has gained many meaningful results.Among them,the rapid development of two-dimensional(2D)materials has become promising candidate materials for sequencing due to their superior characteristics.In addition to the four natural bases,there are many methylation products,which mainly consist methylated bases of cytosine.In the past few years,many studies have shown that abnormal DNA methylation levels are closely related to the occurrence of many cancer diseases.Therefore,the studies on natural DNA sequencing and methylation detection have significant theoretical and potential application values.Using the density functional theory(DFT)and non-equilibrium Green's function method(NEGF),the adsorption interactions between three two-dimensional nanoribbons(silicene,black arsenene,and Ge P₃)and four natural(A,T,G,and C)and four methylated(5-methylcytosine,5-hydroxymethylcytosine,5-formylcytosine and 5-carboxycytosine,abbreviated as 5m C,5hm C,5f C and 5ca C)nucleobases were studied in detail.Based on the experimentally measurable electrical signals,novel schemes about DNA sequencing and methylation recognition were designed.We carried out a series of meaningful works and obtained some valuable results.The main results are briefly summarized as follows:(1)Methylation Detection and DNA Sequencing Based on Adsorption of Nucleobases on Silicene:Compared with graphene,silicene has two prominent advantages:much stronger spin–orbit coupling and better tunability of the band gap due to puckering in its geometry.Moreover,it has compatibility with existing semiconductor techniques and may allow for easier integration with ubiquitous silicon-based microelectronics than graphene.With these characteristics,silicene also shows great potential in molecular sensors.However,to the best of our knowledge,there are no previous reports that investigated methylation recognition by the adsorption of nucleobases on a silicene surface.Therefore,in this part,we examined the potential of silicene nanoribbons for the direct electrical detection of DNA methylation in addition to the sensing of natural nucleobases.Firstly,the geometries of eight bases adsorbed on silicene nanoribbons surfaces were optimized and the electronic properties were analyzed deeply.The results reveal that adenine is physisorbed on the surface of the silicene nanoribbons,while the other seven nucleobases are weakly chemisorbed.Moreover,the adsorption effects of the different nucleobases on the charge transport properties of silicene nanoribbons were clarified by the transmission spectra and density of states.According to the obtained current-voltage characteristics,one electrical detection strategy for methylation and DNA sequencing was proposed.We deduced that it is possible to differentiate between all eight nucleobases using electrical signals at distinct applied bias voltages of 0.5 and 1.0 V.Our results indicate that silicene can serve as a potential candidate for exploring methylation discrimination in addition to DNA sequencing.(2)Methylation Detection and DNA Sequencing Based on Adsorption of Nucleobases on Ge P₃:Ge P₃,a novel two-dimensional layered material composed of Ge and P atoms,has attracted study attention due to its small indirect band gap(0.79 e V),high carrier mobility(10³cm² V^-1 s^-1),and high detection sensitivity to small molecules.In the fourth chapter,the recognition abilities of Ge P₃ nanoribbons to eight nucleobases were clarified.On the basis of this research,the differentiation schemes,based on mismatched base pairs adsorbed on the 2D material(hereinafter referred to as functionalized Ge P₃ nanoribbons)using bases as probes were designed in the fifth chapter.Probes with natural nucleobase should have better biocompatibility compared with other probes.The geometric structures,electronic properties,and charge transport of these adsorption systems were calculated and analyzed.It was found that these bases and base pairs were physically adsorbed on the Ge P₃ nanoribbons through van der Waals forces.According to the obtained I-V curves,it was found that among the eight single bases,four natural bases can be easily identified under a bias of 1.0 V,and base C and its methylated bases can be completely discerned under a bias of 0.2 V.Among the nine mismatched base pairs,four natural base pairs can be distinguished under a bias of 0.8V,and base C and its methylated base pairs can be easy differenced under a bias of 1.0 V.These indicate that our proposed probes improve the sensitivity of Ge P₃ nanoribbons to recognize nucleobases.What's more,according to the transmission spectra and density of states of these adsorption systems,we found that single bases and mismatched base pairs will reduce the conductivity of the pristine nanoribbon,especially the base pair of 5f CT.In addition,Fano resonance exists between the interaction of single bases and base pairs with Ge P₃ nanoribbons.(3)Methylation Detection and DNA Sequencing Based on Adsorption of Nucleobases on black arsenene:The sixth chapter mainly focuses on the recognition of black arsenene nanoribbons to eight natural and methylated nucleobases.Black arsenene,with an indirect band gap of 0.72 e V,high carrier mobility,and good structural stability,is a two-dimensional layered material with a structure similar to black phosphorene.Recently,many studies have shown that black arsenene has high anisotropic sensitivity and good selectivity in molecular sensing field.In this part,the interactions of eight nucleobases with black arsenene nanoribbons were investigated.Through calculating the adsorption geometries and analyzing the electronic properties of the adsorption systems,it can be found that eight bases are also physically adsorbed on the nanoribbons through van der Waals forces,which is the same as the bases physically adsorbed on the black phosphorene nanoribbons reported in the previous literature.Moreover,by analysis the transmission spectrum and the density of states,we can know that eight nucleobases can also make the conductivity of nanoribbon turn down.And the dips in the transmission spectrum and the peak DOS in the projecting DOS of the base are in the same positions,which proves that there is coupling interactions between the bases and the nanoribbons.At last,the calculated I-V curves of the eight adsorption systems show that not only the four natural bases,but also the base C and methylated bases can be fully recognized under a base of 1.4 V.These studies indicate that black arsenene has the better sensitivity to nucleobase molecules compared with silicene and Ge P₃.In conclusion,we found that silicene,Ge P₃ and black arsenene nanoribbons can accurately distinguished nucleobases,so these materials can serve as potential candidates for exploring methylation discrimination in addition to DNA sequencing.In the meanwhile,their recognition abilities are also different.From the obtained results,black arsenene has the better recognition performance for natural and methylated base molecules compared with silicene and Ge P₃.