Daniel Cole

Polarized Protein-Specific Charges from Atoms-in-Molecule Electron Density Partitioning

Louis P. Lee,1 Daniel J. Cole,1,2 Chris-Kriton Skylaris,3 William L. Jorgensen,2 Mike C. Payne,1
1Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK
2Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA
3School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK

Atomic partial charges for use in traditional force fields for biomolecular simulation are often fit to the electrostatic potentials of small molecules and, hence, neglect large-scale electronic polarization. On the other hand, recent advances in atoms-in-molecule charge derivation schemes show promise for use in flexible force fields, but are limited in size by the underlying quantum mechanical calculation of the electron density. Here, we implement the density derived electrostatic and chemical charges method in the linear-scaling density functional theory code ONETEP. Our implementation allows the straightforward derivation of partial atomic charges for systems comprising thousands of atoms, including entire proteins. We demonstrate that the derived charges are chemically intuitive, reproduce ab initio electrostatic potentials of proteins and are transferable between closely-related systems. Simulated NMR data derived from molecular dynamics of three proteins using force fields based on the ONETEP charges are in good agreement with experiment.

Journal of Chemical Theory and Computation 9, 2981 (2013)