The nature of base stacking: a Monte Carlo study


To elucidate the physical origin of the preference of nucleic acid bases for stacking over hydrogen bonding in water, Monte Carlo simulations were performed starting from Watson–Crick structures of the adenine–thymine, adenine–uracil and guanine–cytosine base pairs, as well as from the Hoogsteen adenine–thymine base pair, in clusters comprising 400 and 800 water molecules. The simulations employed a newly implemented Metropolis Monte Carlo algorithm based on the extended cluster approach. All simulations reached stacked structures, confirming that such structures are preferred over the hydrogen-bonded Watson–Crick and Hoogsteen base pairs. The Monte Carlo simulations show the complete transition from hydrogen-bonded base pairs to stacked structures in the Monte Carlo framework. Analysis of the average energies shows that the preference of stacked over hydrogen-bonded structures is due to the increased water–base interaction in these structures. This is corroborated by the increased number of water–base hydrogen bonds in the stacked structures.

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We are grateful to Professor Stefan Grimme for providing us with BLYP-D3 energies for the AT, AU and GC stacks. TvM and HAF thank EaStCHEM for support via the EaStCHEM Research Computing Facility. TvM and VID acknowledge financial support from the Royal Society through an International Joint Project grant.

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Correspondence to Tanja van Mourik.

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Dedicated to Professor Akira Imamura on the occasion of his 77th birthday and published as part of the Imamura Festschrift Issue.

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Dailidonis, V.V., Danilov, V.I., Früchtl, H.A. et al. The nature of base stacking: a Monte Carlo study. Theor Chem Acc 130, 859–870 (2011).

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  • Monte Carlo
  • Cluster
  • Base stacking
  • Hydrophobic interaction