A pseudobond approach to combining quantum mechanical and molecular mechanical methods

Abstract

A major challenge for combined quantum mechanical and molecular mechanical methods (QM/MM) to study large molecules is how to treat the QM/MM boundary that bisects some covalent bonds. Here a pseudobond approach has been developed to solve this problem for ab initio QM/MM calculations: a one-free-valence atom with an effective core potential is constructed to replace the boundary atom of the environment part and to form a pseudobond with the boundary atom of the active part. This pseudobond, which is described only by the QM method, is designed to mimic the original bond with similar bond length and strength, and similar effects on the rest of the active part. With this pseudobond approach, some well-known deficiencies of the link atom approach have been circumvented and a well-defined potential energy surface of the whole QM/MM system has been provided. The construction of the effective core potential for the pseudobond is independent of the molecular mechanical force field and the same effective core potential is applicable to both Hartree–Fock and density functional methods. Tests on a series of molecules yield very good structural, electronic, and energetic results in comparison with the corresponding full ab initio quantum mechanical calculations.

Free Energies of Chemical Reactions in Solution and in Enzymes with Ab Initio Quantum Mechanics/Molecular Mechanics Methods

“…In contrast, two other approaches, namely the pseudobond method [13,47] and the frozen local orbital method [48,19,49,20,50], do not bear such problems. In the pseudobond method, the MM-bonded QM atoms are assigned a special basis set and an effective core potential that is designed to mimic the correct covalent bonding involving the boundary QM atoms.…”

“…Several approaches have been developed [11] [13,47] [48,19,49,20,50]. Traditionally, "link" hydrogen atoms are added to the MM-bonded QM atoms to saturate the valence orbital of the QM subsystem [11].…”

“…Direct inclusion of those MM point charges in the QM effective Hamiltonian can cause charge penetration and off-balance polarization of the QM electrons. To address this problem, rescaling of the MM charges [13] or smearing the MM charges by Gaussian distributions have been developed [57].…”

“…The other type of QM/MM calculation [13,14,15,16,17,18,19,20,7] uses ab initio QM via wavefunction theory or density functional theory. DFT is the most popular approach because of the optimal balance of efficiency and accuracy [21,22,23].…”

Applying Grid Computing to the Parameter Sweep of a Group Difference Pseudopotential

“…Zhang et al recently developed such a "pseudobond" approach by adding an effective core potential (ECP) to a fluorine atom to model the methyl group in a carboncarbon single bond [1]. Their parameterizations were done for the ethane molecule (C ps = F with pseudopotential), then tested on ethane derivatives, and later applied to enzymatic reactions.…”