1.14*CM1A-LBCC: Localized Bond-Charge Corrected CM1A Charges for Condensed-Phase Simulations

The quality of the 1.14*CM1A and 1.20*CM5 charge models was evaluated for calculations of free energies of hydration. For a set of 426 neutral molecules, 1.14*CM1A and 1.20*CM5 yield MADs of 1.26 and 1.21 kcal/mol, respectively. The 1.14*CM1A charges, which can be readily obtained for large systems, exhibit large deviations only for a subset of functional groups. The results for these cases were systematically improved using localized bond charge corrections (LBCC) by which offsetting adjustments are made to the partial charges for atoms in specified bond types. Only 19 LBCCs were needed to yield 1.14*CM1A-LBCC charges that reduce the errors for the 426 Delta G(hyd) values to only 0.61 kcal/mol. The modified charge method was also tested in computation of heats of vaporization and densities for pure organic liquids, yielding average errors of 1.40 kcal/mol and 0.024 g/cm(3), similar to those for 1.14*CM1A.