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

ABSTRACT: 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-profi

SUBMITTER: Chandorkar S 

PROVIDER: S-EPMC8196565 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature