Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Improving the Amber RNA force field
We describe a new method for improving the parameters of the Amber force field for RNA by fitting to energies and forces from quantum chemistry calculations. Parameters for the Amber force field currently in use were obtained from sources such as vibrational frequencies and crystal data for bonded and van der Waals parameters and QM calculations for the partial charges. We are pioneering a new approach in which we keep the Amber force field functional form, but fit all the parameters simultaneously to reproduce the energy and forces determined by a high-level density functional theory (DFT) calculation. The procedure is as follows. First, we assemble a collection of structures that are used for fitting. We use 10,000 covalently bonded two-nucleotide structures that were obtained from high-resolution crystal structures and molecular dynamic simulations. Next, we perform B97D-D3/AUG-cc-pVTZ calculations in an implicit solvent model on these structures to calculate their energies and forces. Finally, we fit the QM energy and force to determine the parameters.
Currently, we are focusing on fitting backbone dihedral parameters using linear regression. We used umbrella sampling to determine potentials of mean force along the dihedral angles, and the free energy changes of the newly fitted torsion parameters better agree with the population of conformations observed in the protein data bank than the conventional parameters. Molecular dynamic simulation performed on a set of hairpin loops and duplexes with the new parameter set shows similar behavior as of the current Amber force field.
Asaminew H. Aytenfisu
Department of Biochemistry & Biophysics and Center for RNA Biology