Lijun Liang

Effects of Graphene Nanopore Geometry on DNA Sequencing

In this Letter we assess the effect of graphene nanopore geometries on DNA sequencing by considering DNA fragments including A, T, C, G, and 5-methylcytosine (MC) pulled out of graphene nanopores of different geometries with diameters down to ∼1 nm. Using steered molecular dynamics simulations it is demonstrated that the bases (A, T, C, G, and MC) can be indentified at single-base resolution through the characteristic peaks on the force profile in a circular graphene nanopore but not in nanopores with other asymmetric geometries. Our study suggests that the graphene nanopore surface should be modified as symmetrically as possible in order to sequence DNA by atomic force microscopy or optical tweezers.

Molecular Dynamics Simulation on Stability of Insulin on Graphene

The adsorption dynamics of a model protein (the human insulin) onto graphene surfaces with different sizes was investigated by molecular dynamics simulations. During the adsorption, it has different effect on the stability of the model protein in the fixed and non-fixed graphene systems. The tertiary structure of the protein was destroyed or partially destroyed, and graphene surfaces shows the selective protection for some -helices in non-fixed systems but not in fixed systems by reason of the flexibility of graphene. As indicated by the interaction energy curve and trajectory animation, the conformation and orientation selection of the protein were induced by the properties and the texture of graphene surfaces. The knowledge of protein adsorption on graphene surfaces would be helpful to better understand stability of protein on graphene surfaces and facilitate potential applications of graphene in biotechnology.

Peptide encapsulation regulated by the geometry of carbon nanotubes.

In this work the encapsulation of an α-helical peptide in single carbon nanotubes (CNTs) with similar diameter and length but different geometry (armchair and zigzag) was investigated through molecular dynamics simulations and free energy calculations. Our simulation results showed that in vacuo it makes no evident difference whether the investigated peptide is encapsulated in armchair or zigzag CNTs; however, in aqueous solution the armchair CNT encapsulates the peptide remarkably easier than the zigzag CNT does. A detailed analysis revealed that the equilibrium conformation of the water molecules inside the CNTs with varying geometry mediates the peptide encapsulation. It suggests that the water molecules play an important role in regulating behaviors of biomolecules in bio-systems. Then the impact of the CNT geometry on the conformational changes of the confined peptide was studied. Analyses of secondary structures showed the α-helix of the peptide could be better maintained in the zigzag CNT.

Charge-tunable absorption behavior of DNA on graphene

Solving the problem of DNA sticking to graphene is very important for the use of graphene in DNA sequence or other DNA sensor technology. In this study, we use molecular dynamics simulation to demonstrate that DNA tends to adsorb on pristine neutralized graphene rather than on graphene with negative charge. This property of graphene could be charge-tuned from DNA-philic to DNA-phobic, and the property is evaluated by the contact angle of DNA absorbed the on graphene surface. With a negative charge, graphene is prone to be DNA-phobic; with a positive charge, or without a charge, it is likely to be DNA-philic. The translocation time of DNA on a graphene nanopore was greatly extended if the graphene nanopore is functionalized by a negative charge. This study could help us to better design a promising device for DNA sequencing by graphene nanopores.

Dispersion of Graphene Sheets in Aqueous Solution by Oligodeoxynucleotides

Applications of graphene sheets in the fields of biosensors and biomedical devices are limited by their insolubility in water. Consequently, understanding the dispersion mechanism of graphene in water and exploring an effective way to prepare stable dispersions of graphene sheets in water is of vital importance for their application in biomaterials, biosensors, biomedical devices, and drug delivery. Herein, a method for stable dispersion of graphene sheets in water by single-stranded oligodeoxynucleotides (ssODNs) is studied. Owing to van der Waals interactions between graphene sheets, they undergo layer-to-layer (LtL) aggregation in water. Molecular dynamics simulations show that, by disrupting van der Waals interaction of graphene sheets with ssODNs, LtL aggregation of graphene sheets is prevented, and water molecules can be distributed stably between graphene sheets. Thus, graphene sheets are dispersed stably in water in the presence of ssODNs. The effects of size and molarity of ssODNs and noncovalent modification of graphene sheets are also discussed.

Theoretical studies on the dynamics of DNA fragment translocation through multilayer graphene nanopores

Motivated by several potential advantages over common sequencing technologies, solid-state nanopores, in particular graphene nanopores, have recently been extensively explored as biosensor materials for DNA sequencing. Studies carried out on monolayer graphene nanopores aiming at single-base resolution have recently been extended to multilayer graphene (MLG) films, indicating that MLG nanopores are superior to their monolayer counterparts for DNA sequencing. However, the underlying dynamics and current change in the DNA translocation to thread MLG nanopores remain poorly understood. In this paper, we report a molecular dynamics study of DNA passing through graphene nanopores of different layers. We show that the DNA translocation time could be extended by increasing the graphene layers up to a moderate number (7) under a high electric field and that the current in DNA translocation undergoes a stepwise change upon DNA going through an MLG nanopore. A model is built to account for the relationship between the current change and the unoccupied volume of the MLG nanopore. We demonstrate that the dynamics of DNA translocation depends specifically on the interaction of nucleotides with the graphene sheet. Thus, our study indicates that the resolution of DNA detection could be improved by increasing the number of graphene layers in a certain range and by modifying the surface of the graphene nanopores.

Interaction of P-glycoprotein with anti-tumor drugs: the site, gate and pathway

Understanding the mechanism and pathway of anti-cancer drugs to be pumped out by P-glycoprotein (P-gp) in cancer cell is very important for the successful chemotherapy. P-gp is a member of ATP-binding cassette (ABC) transporters. In this study, random accelerated molecular dynamics (RAMD) simulation was used to explore the potential egress pathway of ligands from the binding pocket. This could be considered as a reverse process of drug binding. The most possible portal of drugs to dissociate is TM4/TM6, which is almost the same for different drugs, such as paclitaxel and doxorubicin. The interactions in the binding site are found to be remarkably stronger than that outside of the binding site. The results were suggested by the free energy calculation between P-gp and different drugs from metadynamics simulation. All the results indicate that the flexibility of inner residues, especially the residue Phe339, is very important for the drugs to access the binding site.

A molecular dynamics study on pH response of protein adsorbed on peptide-modified polyvinyl alcohol hydrogel

The interactions between proteins and functional biomaterials under different physical and environmental conditions need to be understood when designing biomedical devices. Herein, we present a molecular dynamics simulation study of the fragment antigen-binding (Fab) of trastuzumab (a monoclonal antibody) and its complex with a peptide-modified polyvinyl alcohol (PVA) hydrogel at different pH values. Consistent with experiments, PVA when modified by charged ligands does shrink as a direct response to a drop in the pH. The protein maintains a stable conformation when adsorbed on the hydrogel matrix with a varied pH, showing no signs of denaturation in all simulated systems, suggesting that peptide-grafted PVA is a good biocompatible material. Under neutral conditions, the hydrogel alone stabilizes the interactions between the protein and the peptide ligands. Strikingly under acidic conditions the protein-ligand interactions are disrupted by a collective protonation of ligands. A sharp decrease in the interaction energies, accompanied by the sudden increase of the protein-ligand distance, indicates a rapid pH response in the protein-hydrogel complex. This will be important in protein delivery and purification. The effect of pH on the interactions and the dynamics of the protein and the sudden pH response of the hydrogel at the atomic level present a new functional perspective in developing new hydrogels with desirable properties.

On the loading mechanism of ssDNA into carbon nanotubes

Understanding of the mechanism and dynamics of DNA loading into carbon nanotubes (CNTs) is very important for the promising applications of CNTs in DNA sequencing, drug delivery and gene delivery systems etc. In this work, the loading mechanism and dynamics of different ssDNA oligomers into single-walled carbon nanotubes (SWNTs) was investigated through molecular dynamics simulations, steered molecular dynamics simulation and binding free energy calculations. Our simulation results showed that the loading of different ssDNA oligomers into the zigzag SWNT is much easier than for the armchair SWNT. Confined in both zigzag and armchair type SWNTs, ssDNA oligomers have a helical structure and their bases adapt the orientation parallel to the interior wall. From detailed analysis of the interaction energy, potential of mean force (PMF) of the unloading process and nucleotide binding free energy, our results show that the chirality of SWNTs has a large effect on the binding strength of nucleotides, and hence affects the loading dynamics of ssDNA into SWNTs.

Molecular dynamics simulations indicate that DNA bases using graphene nanopores can be identified by their translocation times

The improvement of the resolution of DNA sequencing by nanopore technology is very important for its real-life application. In this paper, we report our work on using molecular dynamics simulation to study the dependence of DNA sequencing on the translocation time of DNA through a graphene nanopore, using the single-strand DNA fragment translocation through graphene nanopores with diameters down to ∼2 nm as examples. We found that A, T, C, and G could be identified by the difference in the translocation time between different types of nucleotides through 2 nm graphene nanopores. In particular, the recognition of the graphene nanopore for different nucleotides can be greatly enhanced in a low electric field. Our study suggests that the recognition of a graphene nanopore by different nucleotides is the key factor for sequencing DNA by translocation time. Our study also indicates that the surface of a graphene nanopore can be modified to increase the recognition of nucleotides and to improve the resolution of DNA sequencing based on the DNA translocation time with a suitable electric field.