Coarse-Grained RNA Model for the Martini 3 Force Field

Abstract

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 timestep 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. SignificanceThis research introduces a new coarse-grained model for explicit water MD simulations of RNA compatible with Martini 3 software. The model demonstrates improved agreement with both all-atom simulations and experimental data, enabling more accurate and computationally efficient simulations of large RNA-protein complexes. This advancement facilitates the study of RNA and RNA-protein interactions, allowing for the modeling of larger biological complexes and paving the way for more efficient simulations of RNA systems across various fields, including therapeutics, molecular biology, and synthetic biology, where understanding RNA interactions is crucial for developing biomedical applications and advancing fundamental research.