title: Performance Evaluation of the Three-Layer ONIOM Method:  Case Study for a Zwitterionic Peptide.
abstract: The performance of the three-layer ONIOM method was systematically investigated by comparing the optimized geometries and calculated deprotonation energy of a zwitterionic peptide molecule, NH3(+)-CH(n)Bu-CO-NH-CH2-CO-NH-CH(n)Bu-COO(-), using all possible combinations of B3LYP/6-31G* as the high-level quantum (HQ), AM1 as the low-level quantum (LQ), and Amber as the MM method. Results show that the three-layer ONIOM(HQ:LQ:MM) method, which includes a medium-level quantum method in the middle system to take into account the electronic effects of the middle layer and to keep the problematic QM-MM boundary away from the action region, is more reliable and more stable than the QM:MM:MM or generic QM/MM method and is the best compromise between accuracy and computational cost.
authors.affiliation: Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, Georgia 30322, and Gaussian, Inc., 340 Quinnipiac Street, Building 40, Wallingford, Connecticut 06492.
authors.forename: Keiji
authors.initials: K
authors.lastname: Morokuma
authors.affiliation: Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, Georgia 30322, and Gaussian, Inc., 340 Quinnipiac Street, Building 40, Wallingford, Connecticut 06492.
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, Georgia 30322, and Gaussian, Inc., 340 Quinnipiac Street, Building 40, Wallingford, Connecticut 06492.
authors.forename: Thom
authors.initials: T
authors.lastname: Vreven