Coarse-grained RNA model for the Martini 3 force field.

In this work, we developed a coarse-grained model for RNA that is compatible with the Martini 3 force field. The model is parameterized following the Martini philosophy combining the top-down and bottom-up approaches. The nonbonded interactions in the model are derived from the partitioning of nucleobases between polar and nonpolar solvents, along with calculations of the potential of mean force between bases. For bonded interactions, parameters were refined based on atomistic simulations of double-stranded RNA. Additionally, an elastic network was incorporated to maintain the structural integrity of complex RNA molecules, such as transfer RNA, and other specific RNA configurations. We present the implementation of the Martini 3 RNA model and demonstrate its ability to capture the properties of individual bases, single-stranded RNA, double-stranded RNA, and RNA-protein complexes. Compared to the Martini 2 version, the current model offers several key advantages. It is fully compatible with the updated Martini 3 force field, exhibits greater numerical stability-allowing for the successful simulation of larger RNA-protein complexes, such as ribosomes, using the standard Martini time step of 20 fs-and it demonstrates improved agreement with all-atom models and experimental data. This new RNA model enables realistic large-scale explicit-solvent molecular dynamics simulations of complex RNA-containing systems.