Exploring RNA structure and dynamics through enhanced sampling simulations

TL;DR

This paper reviews how enhanced sampling simulations extend the timescale of RNA molecular dynamics, enabling detailed exploration of RNA structural dynamics, interactions, and catalytic pathways.

Contribution

It provides a comprehensive overview of enhanced sampling techniques applied to RNA, highlighting technical considerations and future perspectives.

Findings

Enhanced sampling methods improve exploration of RNA conformational landscapes.

These techniques facilitate study of ion/ligand interactions with RNA.

They aid in understanding RNA catalytic mechanisms.

Abstract

RNA function is intimately related to its structural dynamics. Molecular dynamics simulations are useful for exploring biomolecular flexibility but are severely limited by the accessible timescale. Enhanced sampling methods allow this timescale to be effectively extended in order to probe biologically-relevant conformational changes and chemical reactions. Here, we review the role of enhanced sampling techniques in the study of RNA systems. We discuss the challenges and promises associated with the application of these methods to force-field validation, exploration of conformational landscapes and ion/ligand-RNA interactions, as well as catalytic pathways. Important technical aspects of these methods, such as the choice of the biased collective variables and the analysis of multi-replica simulations, are examined in detail. Finally, a perspective on the role of these methods in the characterization of RNA dynamics is provided.