The Amber empirical force field is the major workhorse of modern biomolecular simulation packages. However, tuning its parameters to the properties of biological materials represents a major methodological and computational challenge, due to the size of the required petascale-level simulations. This work employs a combination of experimental data, quantum chemistry calculations of finite systems, and large-scale RMG DFT-level simulations of a crystal of Guanine to generate an extended set of data for refinement of the empirical force field. Simultaneous charge fitting to the electrostatic potential of multiple clusters incorporates the condensed phase effect into the empirical parameters. The created extensive dataset of dimer, trimer and tetramer clusters includes configurations that probe the curvature of the potential energy profile of the crystal in the vicinity of its thermodynamic minimum that are not directly accessible from experiment. These runs, along with the Lennard-Jones parameter sweep, require petascale compute capability.
