A METHOD OF COMBINED QUANTUM-MECHANICAL (QM) MOLECULAR MECHANICS (MM)TREATMENT OF LARGE POLYATOMIC SYSTEMS WITH CHARGE-TRANSFER BETWEEN THE QM AND MM FRAGMENTS

For large molecular systems where neither quantum mechanical (QM) nor molecular mechanics (MM) calculations, applied separately, can solve t he problem, we worked out a method of combined QM/MM calculations with an electronically transparent interface between the quantum and class ical fragments. Three necessary conditions of (1) fragmentation, (2) i nterfragment self-consistency, and (3) QM-MM continuity are formulated and satisfied by (a) cutting the system on a 2s2p atom (border atom) that participates with its hybridized orbitals in both fragments and d oes not serve as a pi bridge between them, (b) introducing an intermed iate fragment which is treated by both QM (electronic structure) and M M (geometry optimization), and (c) using a special iterative procedure of double (intrafragment and interfragment) self-consistent (DSC) cal culations which realizes the electronically transparent interface and charge transfers between the fragments. The method is implemented in a package of computer programs based on INDO/1 for QM calculations, imp roved IEH method (ICONC) for the DSC procedure, and SYBYL for the MM t reatment, all packages modified accordingly. The calculation of a larg e molecular system-iron picket-fence porphyrin-yielded results in good agreement with the X-ray determined structure. The charge transfers b etween the fragments are significant, confirming the importance of ele ctronic transparency of the QM/MM interface. The similar to 0.4 Angstr om out-of-plane position of the iron atom with respect to the porphyri n ring is a quantum effect which cannot be reproduced by pure MM treat ment. (C) 1997 John Wiley & Sons, Inc.