A GENERALIZED HYBRID ORBITAL (GHO) METHOD FOR THE TREATMENT OF BOUNDARY ATOMS IN COMBINED QM MM CALCULATIONS/

A generalized hybrid orbital (GHO) method has been developed at the se miempirical level in combined quantum mechanical and molecular mechani cal (QM/MM) calculations. In this method, a set of hybrid orbitals is placed on the boundary atom between the QM and MM fragments, and one o f the hybrid orbitals participates in the SCF calculation for the atom s in the QM region. The GHO method provides a well-defined potential e nergy surface for a hybrid QM/MM system and is a significant improveme nt over the ''link-atom'' approach by saturating the QM valencies with hydrogen atoms. The method has been tested on small molecules and yie lds reasonable structural, energetic, and electronic results in compar ison with the results of the corresponding QM and MM approximations. T he GHO method will greatly increase the applicability of combined QM/M M methods to systems comprising large molecules, such as proteins.