Adjusted Connection Atoms for Combined Quantum Mechanical and Molecular Mechanical Methods

Abstract

Connection atoms are proposed as an alternative to link atoms in semiempirical hybrid calculations that divide a system at a C−C single bond into a quantum mechanical (QM) and a molecular mechanical (MM) region. A connection atom interacts with the other QM atoms as a specially parametrized QM atom, and with the other MM atoms as a standard carbon MM atom. Detailed definitions of these interactions are given for three QM/MM coupling models (A mechanical embedding, B/C electronic embedding without/with MM polarization). Semiempirical connection atom parameters are derived for three standard methods (MNDO, AM1, PM3) such that the adjusted connection atoms closely reproduce the geometrical and electronic properties of methyl groups. The corresponding deviations are generally smaller than the intrinsic errors of these methods. QM/MM test calculations on proton affinities confirm the usefulness of the adjusted connection atoms, particularly in coupling model B. Connection atoms are conceptually superior to link atoms in that they do not introduce extra centers and thus lead to well-defined potential surfaces. In addition, they allow an improved semiempirical description of the QM/MM interactions

QM/MM: what have we learned, where are we, and where do we go from here?

“…The first is the so-called link atom approach, where a link atom is used to saturate the dangling bond at the "frontier atom" of the PS. This link atom is usually taken to be a hydrogen atom, [34,39,52,72,106,116,119] or a parameterized atom, e.g., a one-free-valence atom in the "connection atom" [70], "pseudobond" [82], and "quantum capping potential" [111] schemes, which involve a parameterized semiempirical Hamiltonian [70] or a parameterized effective core potential (ECP) [82,111] adjusted to mimic the properties of the original bond being cut. The second class of QM/MM methods consists of methods that use localized orbitals at the boundary between the PS and SS.…”

“…At such a short distance, the validity of using a point charge to represent the distribution of electron density is questionable. Special treatments are applied to the MM charges near the boundary so as to avoid this unphysical polarization [33,44,70,71,82,93,110,124]. We will discuss this problem in more detail later in Sect.…”

Simulating enzyme reactions: Challenges and perspectives

“…These include methods based upon hybrid orbitals 51,55,56 and those that use pseudoatoms. 57 Although these methods are more elegant in that they dispense with the fictitious link atoms in the QM region, they have not yet been shown to be consistently better than the newer link atom approximations, 58,59 which are more versatile and, in comparison to the hybrid orbital methods, simpler to implement. The situation is less clear with ab initio QM/MM potentials for which link atom, 60, 61 hybrid orbital, 62 -65 and pseudoatom 66 methods have all been developed.…”

Understanding Enzyme Catalysis Using Computer Simulation

“…66 Alternative approaches do not involve addition or change of atom types, but a special treatment of the electronic orbitals is employed for the QM/MM boundary atoms. In the local frozen orbital approach, 49,67 one singly occupied orbital is defined to be along the truncated bond that is neglected (i.e., frozen) in the wavefunction calculation.…”