Because biological ionic channels play a key role in cellular transport phenomena, they have attracted extensive research interest for the design of biomimetic nanopores with high permeability and selectivity in a variety of technical applications. Inspired by the structure of K(+) channel proteins, we designed a series of oxygen doped graphene nanopores of different sizes by molecular dynamics simulations to discriminate between K(+) and Na(+) channel transport. The results from free energy calculations indicate that the ion selectivity of such biomimetic graphene nanopores can be simply controlled by the size of the nanopore; compared to K(+), the smaller radius of Na(+) leads to a significantly higher free energy barrier in the nanopore of a certain size. Our results suggest that graphene nanopores with a distance of about 3.9 Å between two neighboring oxygen atoms could constitute a promising candidate to obtain excellent ion selectivity for Na(+) and K(+) ions.
P-glycoprotein (P-gp) pumps a broad range of structurally diverse anti-cancer drugs out of cancer cells. Therefore, multi-drug resistance (MDR) in chemotherapy closely correlates with P-gp. However, how this single transport system recognizes different substrates remains unclear. In this study, we attempt to uncover the mechanism of substrate promiscuity of P-gp by atomistic molecular dynamics simulations. Results indicate that different drugs like paclitaxel and doxorubicin approach the putative binding site of P-gp, and the inner residues are found to be important in this process. An obstacle-overcoming process was observed, illustrating that the inner residues are flexible. Interaction energy calculations suggest that the inner residues possess high affinity toward substrates. The cavity of adaptability to accommodate different drugs would help explain why P-gp has so many different substrates.
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.
We designed a series of porous graphene as the separation membrane for hydrogen gas in coal gas. The permeation process of different gas molecules (H2, CO, CH4, and H2S) in porous graphene was evaluated under the atmospheric pressure and high pressure conditions. Our results indicate the hydrogen permeability and selectivity could be tuned by the size and the shape of the porous graphene. For graphene with bigger pores, the selectivity for hydrogen gas could decrease. In the porous graphene with same pore area, the hydrogen gas selectivity could be affected by the shape of the pore. The potential of mean force (PMF) of different gases to pass through a good separation candidate was calculated. The order of PMF for different gases to pass through the good separation candidate is H2 < CO < CH4 ≈ H2S, which is also confirmed by the first-principle density function theory (DFT) calculation.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.