2020

Journal of Chemical Information and Modeling

Rocznik: 2020 | Tom: 60 | Numer: 10

artykuł naukowy

angielski

EN There are only four derivatives of pseudouridine (Psi) that are known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences of pseudouridylation and further modifications using replica exchange molecular dynamics simulations at the nucleoside level, and the simulated conformational preferences were compared with the available experimental (NMR) data. We found that the existing AMBER FF99-derived parameters for these nucleosides did not reproduce the observed experimental features and while the recommended bsc0 correction could be combined with these parameters leading to an improvement in the description of sugar pucker distributions, the chi(OL3) correction could not be applied to these nucleosides as such because of base isomerization. On the other hand, the revised chi torsion parameters (chi(IDRP)) for Psi developed earlier by us (Deb, I., et al. J. Comput. Chem., 2016, 37, 1576-1588) in combination with the AMBER provided parameters and the revised gamma torsion parameters generated conformational distributions, which generally were in better agreement with the experimental data. A significant shift of the distribution of base orientation toward the syn conformation was observed with our revised parameter sets compared to the large excess of anti conformation predicted by the FF99 parameters. Overall, our observations indicated that our revised set of parameters (chi(IDRP)) for Psi were also able to generate conformational distributions for all of the derivatives of Psi in better agreement with the experimental data.

4995 - 5002

10.1021/acs.jcim.0c00369

https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.0c00369

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