Divalent Ion Dependent Conformational Changes in an RNA Stem-Loop Observed by Molecular Dynamics.

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Biophysics

Background:

• Magnesium ions (Mg2+) are crucial for RNA structure and function.
• Accurate modeling of Mg2+ is essential for simulating RNA conformational dynamics.
• Previous studies have highlighted challenges in representing ion-RNA interactions.

Purpose of the Study:

• To compare the performance of five different Mg2+ ion models in molecular dynamics simulations.
• To evaluate the ability of these models to capture an experimentally observed RNA conformational shift.
• To identify potential artifacts in Mg2+-RNA interactions predicted by different models.

Main Methods:

• Performing microsecond-length unrestrained molecular dynamics simulations.
• Utilizing five distinct Mg2+ ion models with varying parametrization and potential forms.
• Analyzing RNA-Mg2+ interactions, including chelation and solvation effects.
• Comparing simulation results against experimentally determined conformational shifts.

Main Results:

• All five Mg2+ models showed similar behavior when RNA adopted its folded conformation.
• Three of the five models exhibited Mg2+ chelation to RNA, with the 12-6-4 model showing likely artifactual binding.
• RNA-Mg2+ interactions through first-shell water molecules were well-described by modern parameters.
• The spontaneous conformational shift from Mg2+-free to Mg2+-associated RNA structure was observed.

Conclusions:

• Modern Mg2+ models, with few exceptions, can accurately describe RNA-Mg2+ interactions and conformational dynamics.
• Careful selection of Mg2+ models is necessary to avoid simulation artifacts, such as oversampled directed chelation.
• These findings advance the accurate computational study of RNA structure and ion-dependent processes.