Combining simulations and experiments to investigate RNA dynamics

Abstract

Conformational dynamics is crucial for ribonucleic acid (RNA) function. Techniques such as nuclear magnetic resonance, cryo-electron microscopy, small-and wide-angle X-ray scattering, chemical probing, or even thermal denaturation experiments probe RNA dynamics at different time and space resolutions. Their combination with accurate atomistic molecular dynamics (MD) simulations paves the way for quantitative and detailed studies of RNA dynamics. First, experiments provide a quantitative validation tool for MD simulations. Second, available data can be used to refine simulated structural ensembles to match experiments. Finally, comparison with experiments allows for improving MD force fields that are transferable to new systems for which data is not available. Here we review the recent literature and provide our perspective on this field.

Internal Normal Mode Analysis applied to RNA flexibility and conformational changes

“…13,14 In this context, predicting both the structure and structural transitions and conformational changes linked to the interactions is very important, particularly in view of the increasing use of relatively low-resolution data obtained by small-angle X-ray scattering (SAXS), cryoEM or biochemical probing (for example Selective 2'-Hydroxyl Acylation analyzed by Primer Extension, SHAPE) [15][16][17] and to develop new integrative approaches. [18][19][20][21][22][23][24] Predicting local or global changes in RNA conformations is still very di cult. In some cases, this hinders the prediction of the structure of the complex or the change of RNA folding.…”

“…13,14 In this context, predicting both the structure and structural transitions and conformational changes linked to the interactions is very important, particularly in view of the increasing use of relatively low-resolution data obtained by small-angle X-ray scattering (SAXS), cryoEM or biochemical probing (for example Selective 2’-Hydroxyl Acylation analyzed by Primer Extension, SHAPE) 15–17 and to develop new integrative approaches. 18–24…”