rCGMM: A Coarse-Grained Force Field Embedding Elastic Network for Studying Small Noncoding RNA Dynamics

Short noncoding RNA molecules play significant roles in catalysis, biological regulation, and disease pathways. Their assessment through sequence-based approaches has been a challenge, compounded by the significant structural flexibility accrued from six free backbone torsions per nucleotide. To efficiently study the structure and dynamics of an extensive repertoire of these molecules in a high throughput mode, we have built a coarse-grained force field using one, two, three, and four pseudoatoms to represent the phosphate, sugar, pyrimidines, and purines, respectively. The Boltzmann inversion method was applied to structures of 5 piRNA, 8 miRNA, and 13 siRNA from the Nucleic Acid Database (NDB) to estimate the initial force field parameters and iteratively optimized through 1 μs molecular dynamics run by comparing against an equivalent all-atom simulation using the CHARMM36 force field. We applied an elastic net to model the hydrogen bond network stabilizing the local structure for double-stranded cases. A spine using pseudoatoms was calculated for the same from the coarse-grain beads, and all beads within a threshold radial distance were constrained using soft distance potentials. Lennard-Jones and Coulomb's potential function modeled the nonbonded interaction. Benchmarks on 26 molecules compared through root-mean-square deviation graphs against all-atom simulation show close concurrence for single- and double-stranded small noncoding RNA molecules. The rCGMM force field is available for download at https://github.com/majumderS/rCGMM.