Biomolecule Detection Using MoS₂ Nanopores By Computer Simulations

The gene carries the genetic code of life,protein is the expression of the genetic code.Exploring the mystery of them will help us interpret the genetic information,uncover the secrets of life,promote the development of gene therapy and the“Precision Medicine Initiative”,and trigger new medical revolution.This study aims to explore the application of MoS2 nanopore in the detection of biomolecules through molecular dynamics?MD?simulations,which might lead to a wide range of potential applications,such as gene sequencing,protein detection,gene therapy and so on.The design of MoS₂ nanopore detection device helps to overcome the limitations of traditional molecule detection technology and overcome the shortage of graphene nanopore devices.All-atom MD simulations are employed to explore the the feasibility of using MoS₂nanopores for protein sequencing.The study is focused on the biologically significant phenylalanine-glycine repeat peptides?FG-nups?—parts of the nuclear pore transport machinery.Interestingly,FG-nups spontaneously adhere to the MoS₂ surface and exhibit stepwise translocation when subject to a applied bias or a hydrostatic pressure gradient.Reducing the peptide's charge density or increasing the peptide's hydrophobicity is found to decrease the translocation rate.However,unidirectional and stepwise translocation driven by a applied bias is observed even when the ratio of charged to hydrophobic amino acids is as low as 1:8.The translocation of the peptides is found to produce stepwise modulations of the ionic current correlating with the type of amino acids present in the nanopore,suggesting that protein sequencing by measuring ionic current blockades may be possible.In order to explore the performance of Mo-only,S-only and Mixed three types of MoS₂nanopore for the detection of ssDNA,the influence of the interaction between ssDNA and MoS2 surface on the DNA translocation is firstly studied.To quantitatively characterize the ssDNA adsorption,the number of bases adhere to MoS2,the number of contacts and the interaction energies between the bases and MoS₂ are calculated,the order of them all are:poly?dA?₂₀>poly?dT?₂₀>poly?dG?₂₀>poly?dC?₂₀.When using the same transmembrane bias,the rate of ssDNA translocted through the Mo-only nanopore is:ssC>ssG>ssT>ssA,S-only nanopore:ssC>ssT>ssA>ssG,Mixed nanopore:ssC>ssT>ssA>ssG;the speed of ssDNA translocation in these nanopores is:Mo-only>Mixed>S-only.MoS2 membrane has a thickness of 0.65 nm,wich usually contains 1-2 bases in the nanopore,so that MoS₂nanopore possesses high detection accuracy.The nanopore transport of the ssDNA is found to produce stepwise modulations of the nanopore ionic current correlated with the type of bases present in the nanopore.The ionic current changes with the type,number,or structure of the base in the pore.By comparing the translocation traces and ionic current blockades,it is found that the detection accuracy of the Mo-only nanopore is the highest,the mixed nanopore is followed,the S-only nanopore is poor.Steered molecular dynamics?SMD?simulations are performed to study the dynamic process of ssDNA translocating through the MoS₂ nanopore,it is found that the ssDNA transports through the nanopores with a diameter of¹.00 nm in a ratchet-like,base-by-base manner,which can achieve the single-base resolution of DNA sequencing,while passes through larger nanopores in a sliding fashion.The results show that the pulling force profiles exhibits distinct peaks when ssA,ssC,ss G,or ssT passes through the MoS₂ nanopore.The statistical analysis of the peak values of the A,C,G,and T bases,shows that the force peaks follows G>A>T>C.All these four bases have unique characteristic peaks and can be readily distinguished from each other,so the detection accuracy of MoS2 nanopores for these four bases is higher than graphene nanopores.Detection of ssDNA with random sequence by SMD simulations indicates that each base in the DNA strand can be identified and characterized by monitoring and analyzing the characteristic peaks on the pulling force profile.Thus,DNA sequencing can be achieved.In addition,we also discuss the influence of nanopore diameter,pulling speed,and spring constant on the ssDNA translocation.We find that selecting an appropriate nanopore is the prerequisite for single-base resolution,while the selections of the pulling speed and spring constant are also significant.