Progress in modelling electrostatics and polarization through effective multipoles and induced charges

Here we present a method for modeling polarization in hybrid QM/MM calculations. The method, which expresses the induced dipoles as a set of 'induced' charges, is based on the induced dipole approach and methodology for calculating potential-derived point charges from distributed multipole series. Here we assess the importance of explicit polarization in the classical part of a QM/MM system with regard to improving the classical description and the consequent effects on the quantum description. The main advantages of the induced charge approach are that the method is readily interfaced with quantum mechanical methods and that induced charges are more readily interpreted than induced dipoles. The ease of interpretation is illustrated by analysis of the charges involved in dimeric and trimeric hydrogen bonded systems. The method has been validated using two energy decomposition approaches, which show that MM polarization makes a significant and reliable contribution to the QM – MM interaction energy in a hybrid system. The method has been modified to assess the likely effect of QM and MM polarization on docking. Since the lack of polarization is only one of a number of deficiencies in current docking approaches, we have also used connectivity to assess alternative docking poses.