Classical molecular dynamics is a ubiquitous tool in bio-pharmaceutical, chemical, and material sciences. Thousands of research teams Nationwide and across the Globe depend on the Amber force field to conduct computer simulations of important practical applications. Developed in 1994, the Amber force field for nucleic acid bases has not been revised since. The present work extends the Amber parameter optimization protocol to reproduce structure and thermodynamic properties of twelve crystals of five nucleobases. The target training data include enthalpies of sublimation at various temperatures, crystal volume, position of the atoms in the crystal, and key intermolecular distances reproduced within 2% error margin. Further extending that dataset, the project employs an unprecedented database of 161 base-base interaction energies to fine-tune the parameters. Based on experimental geometry of the clusters of bases, the database comprises interaction energies computed using the CCSD(T)/6-311++G** level of theory. Multi-conformational charge fitting to the electrostatic potential of the clusters extracted from the crystal data produces atomic point charges that closely represent the average electrostatic potential that the base creates in the crystals.

Optimization of Amber force field for nucleic acid bases

2019 Spring National Meeting

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