Combining molecular simulations, solution experiments, and AI to investigate biomolecules structural dynamics

RNA modifications have attracted increasing attention due to their crucial roles in various biological processes. These modifications involve biochemical alterations of nucleotides that can impact RNA structure and dynamics.

Despite extensive studies, the use of molecular dynamics (MD) simulations to investigate modified RNA remains limited.

MD simulations are a powerful tool for accessing the structural dynamics of RNA at the atomistic level. The accuracy of these simulations largely depends on the quality of the force-field parameters utilized.

Therefore, it is beneficial to combine simulations with experiments, such as by fitting parameters against experimental data or enforcing experimental averages with ensemble refinement methods.

In this talk the use of ensemble refinement methods are presented, to investigate the structure of a 20-bp RNA helix containing Inosines. The maximum entropy principle, along with advanced enhanced sampling techniques, was used to generate an ensemble of structures compatible with NMR and SAXS data.

The presence of Inosines increased flexibility in the helix and allowed for the observation of sugar puckering in the C2′-endo conformation, which is not expected in ds-RNA.

Speaker: Valerio Piomponi, RIT (Area Science Park)