Structural and functional properties of coding and noncoding RNAs are related to the ubiquitous occurrence of non-canonical or modified RNA residues. Currently, more than 160 naturally occurring post-transcriptionally modified residues are known. Although these modifications are widely involved in such vital physiological processes such as codon-anticodon recognition, RNA folding and stability or epigenetic regulation of gene expression, the mechanisms through which these modifications operate are yet to be clearly understood. Molecular modeling tools have been found to provide extensive and valuable insight in the elucidation of the structure and dynamics of biomolecules. However, application of such tools in this scenario has been rather restricted by the lack of rigorously validated force field parameters corresponding to the modified residues. We shall provide an overview of our work on the limitations of the existing set of parameters for RNA modifications for simulations with AMBER and the results obtained by us in connection with their reoptimization and validation. We shall also report the development of new sets of partial atomic charges and parameters for the glycosidic torsion angle at the individual nucleoside level. The reparameterization was carried out to better describe the glycosidic torsion energy profile obtained from QM calculations by MM calculations. The newly obtained parameters were validated through REMD simulations by comparing the simulated conformational preferences with those obtained from experimental observations.

Developing accurate force field parameters for RNA modifications

ACS Spring Meeting 2021

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