Critical investigation on the pseudobond approach for QM/MM and fragment-based QM methods

Abstract

In mixed quantum mechanical/molecular mechanical and fragment-based quantum chemical calculations an accurate treatment of bonds, which are cut to build the fragments, is greatly desired so that the structural and electronic properties of the fragment resemble the properties of the original molecule as accurately as possible. Many different methods have been proposed in the literature to deal with bond fragmentation. One of these methods, the pseudobond approach of Zhang et al. (J Chem Phys, 1999, 110, 46), is analyzed in this work. Reparameterizations were conducted for different training sets and diviations in various molecular properties were used as the objective function of the optimazation process. Most of these parameterizations, including the original one, show good performance in reproducing the structures of five substituted ethane molecules and 17 amino acids, as well as in the energy calculation of an oligopeptide based on our fragment-based quantum chemical approach: the field-adapted adjustable density matrix assembler. Nevertheless, none of the parameterizations shows significant and consistent improvement over simple capping hydrogen atoms, despite the simplicity of that approach.