D-RESP: Dynamically generated electrostatic potential derived charges from quantum mechanics/molecular mechanics simulations

A scheme is proposed for calculating electrostatic potential (ESP) derived charges from mixed quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations. These charges are fitted to the electrostatic field due to the quantum charge density evaluated on the MM atoms close to the QM system and are restrained to the corresponding Hirshfeld value by a quadratic penalty function. The D-RESP charges estimated by this procedure reproduce the field due to the charge density polarized by the environment and can be obtained as a function of time along a finite temperature molecular dynamics trajectory with essentially no computational overhead with respect to a standard QM/MM calculation. The fluctuation of the D-RESP values in a finite temperature run provide information about the importance of polarization effects and thus allow for a direct comparison of the relative performance of polarizable versus non polarizable point charge models. Moreover, the D-RESP charges estimated by this procedure can be used as a simple and straightforward indicator of the chemical state of the system.