Abstract
DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring.
Highlights
We simulated the pulling-forward and following pulling-away processes to confirm the affinity of the different biomarkers with different DNA nucleotides
We studied the interaction between four single DNA nucleotides (A, G, C, and T) on both ssDNA and dsDNA with acetone, ethanol, H2S and HCl
In SMD simulation, the center-of-mass of small molecules was pulled at a certain velocity towards one particular DNA nucleotide
Summary
We simulated the pulling-forward (binding) and following pulling-away (unbinding) processes to confirm the affinity of the different biomarkers with different DNA nucleotides. Taking ssDNA-acetone system for example (Fig. 9), the absolute value of PMF increased when acetone was pushed away indicating there was an attraction force between acetone and DNA (Fig. 9b). A higher absolute value of PMF when pulling acetone molecule away from DNA means a higher affinity between these two molecules.
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