All-Atom Structure-Based Model of RNA with Explicit Electrostatics and Explicit Treatment of Mobile Ions

Structure-based models (SBM) allow milliseconds effective timescale simulations of large biomolecular assemblies. In an SBM, the prevalent potential energy minima are defined to correspond to native structures. Here, we have developed an all-atom SBM in which non-hydrogen atoms and diffuse ions (K⁺, Cl^-, Mg²⁺) electrostatics are described explicitly. The effective desolvation potentials for ion-ion and ion-RNA interactions are introduced such that solvation is treated implicitly. Excluded volume term and long range Coulomb interaction are also included in the forcefield. To calibrate the model, we simulate RNA Helix 44 and compare various observable quantities with explicit-solvent simulations. Using an iterative refinement protocol, the parameters are optimized to reproduce the potential of mean force obtained from two-microsecond explicit-solvent simulations, until the parameters converge iteratively. This transferable forcefield for ion-ion and ion-RNA interactions are then used in SBM of large assemblies. In an initial application of this model, we show how diffuse ions and the excess ion atmosphere can modulate large-scale conformation dynamics in the ribosome. This opens the door to investigate the role of ions in a wide range of RNA-protein biomolecular assemblies.