RNA carries out a broad range of functions including coding, regulation and expression of genes. Molecular dynamics (MD) simulation can be used to investigate the time evolution of RNA conformations and be used to complement or interpret experimental observations. Amber uses a fixed charge force field model to estimate the potential energy of a molecule from the atomic coordinates. Studies suggest that stacking free energies observed from the Amber OL3 RNA force field are too favorable with respect to the experimental data. The non-bonded interactions are modeled by a Lennard Jones potential and Coulomb's law; these parameters have not been updated since 1995.<br/><br/>We are refitting the Amber nonbonded parameters to potential energies determined by quantum mechanics.  Structures from the Protein Data Bank and MD simulation of RNA duplexes are used to harvest base pairs, base stacks, base-phosphates and base-sugar interactions. These structures were clustered on interatomic distances using density peak clustering and cluster centers obtained were chosen as representative structures. To include the polarization from solvent, charges were fit to represent the time-averaged electrostatic field from solvent sampled through molecular dynamics trajectory of these cluster centers with OPC water. Symmetry adapted perturbation theory calculations (SAPT) were used with these representative structures and solvation charges to measure the non-bonded interaction energy. The non-bonded parameters of the Amber fixed-charge potential form were fit by nonlinear regression to the observed interaction energies.

Refinement of the amber force field for RNA: Improving the description of non-bonded interactions

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