Abstract
Quantum mechanical (QM) and hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations of a recently reported dinuclear mercury(II)-mediated base pair were performed aiming to analyse its intramolecular bonding pattern, its stability, and to obtain clues on the mechanism of the incorporation of mercury(II) into the DNA. The dynamic distance constraint was employed to find initial structures, control the dissociation process in an unbiased fashion and to determine the free energy required. A strong influence of the exocyclic carbonyl or amino groups of neighbouring base pairs on both the bonding pattern and the mechanism of incorporation was observed. During the dissociation simulation, an amino group of an adenine moiety of the adjacent base pair acts as a turnstile to rotate the mercury(II) ion out of the DNA core region. The calculations provide an important insight into the mechanism of formation of this dinuclear metal-mediated base pair and indicate that the exact location of a transition metal ion in a metal-mediated base pair may be more ambiguous than derived from simple model building.
Highlights
Nucleic acids with metal-mediated base pairs have been of interest in the development of functional nanostructures [1] as they feature robustness, programmable hybridization properties and a well-established automated synthesis [2,3]
Cholesky inversion was chosen as the solver of the eigenvalue problem, Density Functional Theory (DFT) based ab initio molecular dynamics simulations were carried out with the CP2K program while Broyden mixing was employed for optimization
Cholesky inversion was chosen as the solver of the eigenvalue problem, while Broyden molecular dynamics simulations carriedwith out awith where for mixingQM/MM
Summary
Nucleic acids with metal-mediated base pairs have been of interest in the development of functional nanostructures [1] as they feature robustness, programmable hybridization properties and a well-established automated synthesis [2,3]. Metal-mediated base pairs provide a convenient means for the site-specific functionalization of nucleic acids with metal ions. They can be formed from canonical nucleobases, with thymine and cytosine being the most prominent natural nucleobases capable of engaging in stable metal-mediated base pairs [4,5,6]. As no empirical structures of the solvated DNA duplex were available, we employed the so-called dynamic distance constraint [55] to find an initial geometry of the DNA in the preferred hydrogen bonding pattern. Free energy simulations are performed to study the stability and possible dissociation paths of the novel DNA, where the neighbouring base pairs influence both the bonding pattern and the inclusion path of mercury(II) into the DNA
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