Occurrence and stability of anion–π interactions between phosphate and nucleobases in functional RNA molecules

Mohit Chawla, Kanav Kalra, Zhen Cao, Luigi Cavallo, Romina Oliva

Research output: Contribution to journalArticlepeer-review


We present a systematic structural and energetic characterization of phosphate(OP)–nucleobase anion…π stacking interactions in RNAs. We observed OP–nucleobase stacking contacts in a variety of structural motifs other than regular helices and spanning broadly diverse sequence distances. Apart from the stacking between a phosphate and a guanine or a uracil two-residue upstream in specific U-turns, such interactions in RNA have been scarcely characterized to date. Our QM calculations showed an energy minimum at a distance between the OP atom and the nucleobase plane centroid slightly below 3 Å for all the nucleobases. By sliding the OP atom over the nucleobase plane we localized the optimal mutual positioning of the stacked moieties, corresponding to an energy minimum below -6 kcal•mol−1, for all the nucleobases, consistently with the projections of the OP atoms over the different π-rings we observed in experimental occurrences. We also found that the strength of the interaction clearly correlates with its electrostatic component, pointing to it as the most relevant contribution. Finally, as OP–uracil and OP–guanine interactions represent together 86% of the instances we detected, we also proved their stability under dynamic conditions in model systems simulated by state-of-the art DFT-MD calculations.
Original languageEnglish (US)
JournalNucleic acids research
StatePublished - Nov 23 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-11-29
Acknowledgements: KAUST baseline research funding (to L.C.); MIUR-FFABR ‘Fondo per il Finanziamento Attività Base di Ricerca’ (to R.O.). Funding for open access charge: KAUST baseline research funding. L.C. and M.C. acknowledge the KAUST Core Labs and Supercomputing Laboratory for providing computational resources on the HPC platform Shaheen II.

ASJC Scopus subject areas

  • Genetics


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