Density molecular mechanics, hybrid

The forcefields discussed in Section 2.1 use energy functions which do not take into account quantum effects. Many important processes are intrinsically quantum mechanical, and thus cannot be modelled classically. SA has been used in con-juction with density functional theory, the Schrodinger equation, chemical reaction dynamics, electronic structure studies, and to optimize linear and nonlinear parameters in trial wave functions. This is important because quantum effects are often embedded in an essentially classical system. This has motivated mixing the classical fields with the quantum potentials in simulations known as quantum mechanic/molecular mechanic hybrids. Including quantum effects is important in the study of enzyme reactions, and proton and electron transport studies. 

Amara, P. V., Volbeda, A., Fontecilla-Camps, J. C. and Field, M. J. A. (1999) Hybrid density functional theory/molecular mechanics study of nickel-iron hydrogenase Investigation of the active site redox states./. Am. Chem. Soc., 121, 4468-77. 

Hypercube, Inc. at http //www.hyper.com offers molecular modeling packages under the HyperChem name. HyperChem s newest version, Hyper-Chem Release 7.5, is a full 32-bit application, developed for the Windows 95, 98, NT, ME, 2000, and XP operating systems. Density Functional Theory (DFT) has been added as a basic computational engine to complement Molecular Mechanics, Semiempirical Quantum Mechanics and ab initio Quantum Mechanics. The DFT engine includes four combination or hybrid functions, such as the popular B3-LYP or Becke-97 methods. The Bio+ force field in HyperChem represents a version of the Chemistry at HARvard using Molecular Mechanics (CHARMM) force field. Release 7.5 of HyperChem updates... 

Pu JZ, JL Gao, DG Truhlar (2004a) Combining self-consistent-charge density-functional tight-binding (SCC-DFTB) with molecular mechanics by die generalized hybrid orbital (GHO) method. J. Phys. Chem. A 108 (25) 5454-5463... 

Pu JZ, JL Gao, DG Truhlar (2005) Generalized hybrid-orbital method for combining density functional theory with molecular mechanicals. ChemPhysChem 6 (9) 1853—1865... 

In a third theoretical model the [FeNi]-hydrogenase from D. gigas is modeled using a hybrid density functional theory-molecular mechanics (DFT/MM) method [92]. In this model approximately 30 atoms of the active site (including the four cysteine residues) are modeled with DFT while molecular mechanics is used for the rest of the atoms within a A radius (about 300 atoms). The next shell includes about 10 000 protein and solvent atoms within 27 A of the active site whose posi-... 

Before delving into the techniques, a semantic excursion seems necessary. First, computational quantum chemistry as used in this chapter reflects the broader definition, referring to any technique that uses computers to model a chemical system via the Schrodinger equation or some approximation thereof this is a catch-all for every ab initio method, semiempirical scheme, and theoretical model chemistry. (Density functional theory also is included, although it does not stringently satisfy this definition, because it enjoys widespread identification with the ab initio methods.) Molecular mechanics, therefore, is not computational quantum chemistry, but its application to hybrid QM/MM methods will be discussed regardless. 

This book starts with seven chapters devoted to methods for the computation of molecular structure molecular mechanics, semiempirical methods, wave function-based quantum chemistry, density-functional theory methods, hybrid methods, an assessment of the accuracy and applicability of these methods, and finally 3D structure generation and conformational analysis. 

There is no evidence that any classical attribute of a molecule has quantum-mechanical meaning. The quantum molecule is a partially holistic unit, fully characterized by means of a molecular wave function, that allows a projection of derived properties such as electron density, quanmm potential and quantum torque. There is no operator to define those properties that feature in molecular mechanics. Manual introduction of these classical variables into a quantum system is an unwarranted abstraction that distorts the non-classical picture irretrievably. Operations such as orbital hybridization, LCAO and Bom-Oppenheimer separation of electrons and nuclei break the quantum symmetry to yield a purely classical picture. No amount of computation can repair the damage. 

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