SEMIEMPIRICAL TREATMENT OF ELECTROSTATIC POTENTIALS AND PARTIAL CHARGES IN COMBINED QUANTUM-MECHANICAL AND MOLECULAR MECHANICAL APPROACHES

A semiempirical treatment of electrostatic potentials and partial char ges is presented. These are the basic components needed for the evalua tion of electrostatic interaction energies in combined quantum mechani cal and molecular mechanical approaches. The procedure to compute elec trostatic potentials uses AM1 and MNDO wave functions and is based on one previously suggested by Ford and Wang. It retains the NDDO approxi mation and is thus both easy to implement and computationally efficien t. Partial atomic charges are derived from a semiempirical charge equi libration model, which is based on the principle of electronegativity equalization. Large sets of ab initio restricted Hartee-Fock (RHF/6-31 G) reference data have been used to calibrate the semiempirical model s. Applying the final parameters (C, H, N, O), the ab initio electrost atic potentials are reproduced with an average accuracy of 20% (AM1) a nd 25% (MNDO), respectively, and the ab initio potential derived charg es normally to within 0.1 e. In most cases our parameterized models ar e more accurate than the much more expensive quasi ab initio technique s, which employ deorthogonalized semiempirical wave functions and have generally been preferred in previous applications. (C) 1996 by John W iley & Sons, Inc.