Occurrence and stability of lone pair-π and OH–π interactions between water and nucleobases in functional RNAs

Kanav Kalra, Suresh Gorle, Luigi Cavallo, Romina Oliva, Mohit Chawla

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Abstract We identified over 1000 instances of water-nucleobase stacking contacts in a variety of RNA molecules from a non-redundant set of crystal structures with resolution ≤3.0 Å. Such contacts may be of either the lone pair-π (lp–π) or the OH–π type, in nature. The distribution of the distances of the water oxygen from the nucleobase plane peaks at 3.5 Å for A, G and C, and approximately at 3.1–3.2 Å for U. Quantum mechanics (QM) calculations confirm, as expected, that the optimal energy is reached at a shorter distance for the lp–π interaction as compared to the OH–π one (3.0 versus 3.5 Å). The preference of each nucleobase for either type of interaction closely correlates with its electrostatic potential map. Furthermore, QM calculations show that for all the nucleobases a favorable interaction, of either the lp–π or the OH–π type, can be established at virtually any position of the water molecule above the nucleobase skeleton, which is consistent with the uniform projection of the OW atoms over the nucleobases ring we observed in the experimental occurrences. Finally, molecular dynamics simulations of a model system for the characterization of water-nucleobase stacking contacts confirm the stability of these interactions also under dynamic conditions.
Original languageEnglish (US)
Pages (from-to)5825-5838
Number of pages14
JournalNucleic Acids Research
Issue number11
StatePublished - May 7 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: L.C. and M.C. acknowledge King Abdullah University of Science and Technology (KAUST) for support and the KAUST Supercomputing Laboratory for providing computational resources of the supercomputer Shaheen II; R.O. thanks MIUR-FFABR (Fondo per il Finanziamento Attivita Base di Ricerca) for funding.
Funding for open access charge: King Abdullah University of Science and Technology.


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