Poster abstracts

Poster number 140 submitted by Anees Mohammed Keedakkatt Puthenpeedikak

Refinement of the Amber Force Field For RNA: Improving the Description of Non-Bonded Interactions

Anees Mohammed Keedakkatt Puthenpeedikakkal (Department of Biochemistry and Biophysics, University of Rochester), Chapin E. Cavender (Department of Biochemistry and Biophysics, University of Rochester), Louis G. Smith (Department of Biochemistry and Biophysics, University of Rochester), Alan Grossfield (Department of Biochemistry and Biophysics, University of Rochester), David H. Mathews (Department of Biochemistry and Biophysics, University of Rochester)

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 forcefield model to estimate the potential energy of a molecule from the atomic coordinates. Studies suggest that stacking free energies observed from the current RNA forcefield 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.
We are fitting the Amber parameters to potential energies determined by quantum mechanics. Structures from the Protein Data Bank and MD simulation of RNA duplexes were used to assemble a database of conformations representing base pairs, base stacks, base-phosphates and base-sugar interactions. We clustered these structures by interatomic distances using density peak clustering, and cluster centers were chosen as representative structures. To include the polarization from solvent, we fit charges 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 estimate the non-bonded interaction energy. We fit the Amber non-bonded parameters for the fixed-charge potential form by nonlinear regression to the observed interaction energies.

Keywords: RNA, forcefield, QM