FCPAC: Fast calculation of partial atomic charges using strictly localized molecular orbitals

Most force fields of molecular mechanics use constant partial atomic charges whereas it is now admitted that those charges strongly vary with the environment. Charge variations are particularly important in hydrogen bonds where polar entities come close together. Moreover, organizing H-bonds in networks, like in secondary structures of proteins, go with cooperative effects which lead to an overall electrostatic stabilization of the system. This is why variable atomic charges are required to correctly mimic these effects. Different methods of charge calculation were developed, most use polarizable dipole or electronegativity equalization. In this work, we propose a semi-empirical method (fast calculation of partial atomic charges (FCPAC)) which derives partial atomic charges from strictly localized molecular orbitals. The approximations enable to treat molecular systems with hundreds of atoms within reasonable delays. Results reported here show that charges calculated with FCPAC are similar to charges derived from Mulliken’s population analysis of a restricted Hartree–Fock wave function using the split valence basis set 6-31G and including polarization orbitals p and d respectively for hydrogen and heavy atoms, RHF/6-31G(d,p). Comparison with ab initio calculation was also performed on a system composed of five formamide molecules disposed in the same geometry as peptide bonds in an α helix. Charges variations are similar and suggest that FCPAC is suitable for quantitative estimation of cooperative effects.