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Article

Multiscale Modeling of Wobble to Watson–Crick-Like Guanine–Uracil Tautomerization Pathways in RNA

Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500 032, India
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Author to whom correspondence should be addressed.
Academic Editors: Neha S. Gandhi, Pramod Nair and Zak Hughes
Int. J. Mol. Sci. 2021, 22(11), 5411; https://doi.org/10.3390/ijms22115411
Received: 31 March 2021 / Revised: 5 May 2021 / Accepted: 9 May 2021 / Published: 21 May 2021
(This article belongs to the Special Issue Advances in Modelling and Simulations of Anionic Molecules)
Energetically unfavorable Watson–Crick (WC)-like tautomeric forms of nucleobases are known to introduce spontaneous mutations, and contribute to replication, transcription, and translation errors. Recent NMR relaxation dispersion techniques were able to show that wobble (w) G•U mispair exists in equilibrium with the short-lived, low-population WC-like enolic tautomers. Presently, we have investigated the wG•U → WC-like enolic reaction pathway using various theoretical methods: quantum mechanics (QM), molecular dynamics (MD), and combined quantum mechanics/molecular mechanics (QM/MM). The previous studies on QM gas phase calculations were inconsistent with experimental data. We have also explored the environmental effects on the reaction energies by adding explicit water. While the QM-profile clearly becomes endoergic in the presence of water, the QM/MM-profile remains consistently endoergic in the presence and absence of water. Hence, by including microsolvation and QM/MM calculations, the experimental data can be explained. For the G•Uenol→ Genol•U pathway, the latter appears to be energetically more favorable throughout all computational models. This study can be considered as a benchmark of various computational models of wG•U to WC-like tautomerization pathways with and without the environmental effects, and may contribute on further studies of other mispairs as well. View Full-Text
Keywords: QM/MM; MD; Watson–Crick; WC-like; mispair; wobble; tautomerization; G•U; reaction energies QM/MM; MD; Watson–Crick; WC-like; mispair; wobble; tautomerization; G•U; reaction energies
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MDPI and ACS Style

Chandorkar, S.; Raghunathan, S.; Jaganade, T.; Priyakumar, U.D. Multiscale Modeling of Wobble to Watson–Crick-Like Guanine–Uracil Tautomerization Pathways in RNA. Int. J. Mol. Sci. 2021, 22, 5411. https://doi.org/10.3390/ijms22115411

AMA Style

Chandorkar S, Raghunathan S, Jaganade T, Priyakumar UD. Multiscale Modeling of Wobble to Watson–Crick-Like Guanine–Uracil Tautomerization Pathways in RNA. International Journal of Molecular Sciences. 2021; 22(11):5411. https://doi.org/10.3390/ijms22115411

Chicago/Turabian Style

Chandorkar, Shreya, Shampa Raghunathan, Tanashree Jaganade, and U. Deva Priyakumar. 2021. "Multiscale Modeling of Wobble to Watson–Crick-Like Guanine–Uracil Tautomerization Pathways in RNA" International Journal of Molecular Sciences 22, no. 11: 5411. https://doi.org/10.3390/ijms22115411

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