Colorimetric aptasensor based on assembly of salt-induced gold nanoparticles (AuNPs) is a promising biosensor. However, the molecular mechanism of the aptasensor is far from being fully understood. Herein, molecular dynamics (MD) simulation was used to investigate molecular interactions in the detection of ochratoxin A (OTA) including the following: (i) the molecular recognition of the anti-OTA aptamer, (ii) OTA-aptamer interactions in monovalent (Na) and divalent (Mg) electrolytes, (iii) the binding mode of citrate on the AuNP surface, (iv) interactions of the aptamer with citrate-capped AuNPs, and (v) a detailed mechanism of the aptasensor. Our MD simulations revealed a specific binding of the OTA-aptamer complex, compared with OTB and warfarin. Compared with Na, Mg ions exerted a more effective attractive force between OTA and anti-OTA aptamer. Three different binding modes of citrate on AuNP surfaces were found. The kinetics of the adsorption of unfolded aptamers onto the citrate-capped AuNP was also elucidated. Most importantly, our MD simulation revealed an insightful analysis of the molecular mechanisms in the AuNP-based aptasensor and paved the way for the design of a novel colorimetric aptasensor for other target molecules, which is not limited to OTA detection.

A visual strategy for 8-oxo-dG monitoring based upon the dispersion of citrate-capped gold nanoparticles has been developed.

The concentration of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in urine or serum is associated with the degree of oxidative damage of DNA and broadly used as a sensitive biomarker for various diseases. However, determination of a low concentration of 8-oxo-dG in biosamples is not an easy task owing to the complexity of coexisting substances. Herein, we design an aptasensor based on aptamer-mediated aggregation of cysteamine-capped gold nanoparticles (Cyst/AuNPs) for the detection of 8-oxo-dG by molecular dynamics simulation. Our simulations reveal that a positively charged Cyst modified onto the surfaces of AuNP exists in two conformers including gauche and trans. The trans conformer was prevalent on the AuNP surfaces and can stabilize AuNPs in the aqueous solution, even in the presence of 8-oxo-dG. Molecular recognition between 8-oxo-dG and the aptamer was demonstrated and bonding between these biomolecules was thoroughly elucidated. During the complex formation, van der Waals stacking interactions between 8-oxo-dG molecules were observed and found to play a significant role in the binding stability. The sensing mechanism of the colorimetric aptasensor was studied and the feasibility study of the proposed aptasensor was assessed by experimental validation. The experimental results are in good agreement with the computational study. Our in silico design can pave the way for, but is not limited to, a highly sensitive aptasensor for the naked-eye detection of 8-oxo-dG.

No abstract

In cancer genomes, DNA methylation results in the formation of a distinct methylation landscape (methylscape) characterized by clustered methylation at regulatory regions separated by extensive intergenic tracks of hypomethylated regions. This methylscape is expressed in the majority of cancer types, thus serving as a universal biomarker for cancer. The aim of the present study was to distinguish between normal and cancer DNA on the basis of their distinct methylscapes using cysteamine-capped gold nanoparticles (Cyst/AuNPs). The signature interactions between cancer DNA and the positively charged AuNPs were revealed by molecular dynamics (MD) simulations and density functional theory (DFT) calculations. Our simulations demonstrate that DNA aggregates in aqueous solution in a methylation-dependent manner, due primarily to the increased hydrophobic force caused by the addition of the methyl group. This suggests that the distinct methylscapes of cancer and normal DNA may result in different agglomerations in aqueous solutions. Cyst/AuNP adsorption patterns on normal and cancer DNA aggregates were also observed to be distinct in MgCl2 solution. Using MD simulations, we discovered that the backbone of oligonucleotides plays a significant role in DNA adsorption onto the gold surface. In addition to that, our DFT calculations indicate that 5-methylcytosine (5-mC) adsorbed on the gold surface has a lower adsorption energy in comparison to cytosine, suggesting that 5-mC is a more favorable site for AuNP adsorption. Due to the methylation-dependent adsorption of Cyst/AuNPs on DNA aggregates, this enables the use of Cyst/AuNPs in cancer screening on the basis of the dispersion of AuNPs adsorbed on DNA aggregates, which is consistent with our experimental validation. This work paves the way for the development of a rapid colorimetric AuNP-based biosensor for methylscape detection that could be used for universal cancer screening.