Theory molecular mechanics methods

RESPONSE FUNCTIONS FOR THE DENSITY FUNCTIONAL THEORY/MOLECULAR MECHANICS METHOD... 

This section considers how to derive the response functions for the density functional theory molecular mechanics method and the derivation of these response functions is similar to the procedure of obtaining density functional theory response functions for molecules in vacuum [58]. For the method and the derivation, we utilize the adiabatic approximation and thereby we assume that vxc[p](r, t) = vxc[p](r). 

One way that molecular mechanics methods have been adapted to transition metal applications is by including one orbital-based term in the force field to describe the metal center. These terms are typically based on semiempirical methods or even some variation of ligand field theory. 

A review of the Journal of Physical Chemistry A, volume 110, issues 6 and 7, reveals that computational chemistry plays a major or supporting role in the majority of papers. Computational tools include use of large Gaussian basis sets and density functional theory, molecular mechanics, and molecular dynamics. There were quantum chemistry studies of complex reaction schemes to create detailed reaction potential energy surfaces/maps, molecular mechanics and molecular dynamics studies of larger chemical systems, and conformational analysis studies. Spectroscopic methods included photoelectron spectroscopy, microwave spectroscopy circular dichroism, IR, UV-vis, EPR, ENDOR, and ENDOR induced EPR. The kinetics papers focused on elucidation of complex mechanisms and potential energy reaction coordinate surfaces. 

T. Vreven, K. S. Byun, I. Komaromi, S. Dapprich, J. A. Montgomery Jr., K. Morokuma and M. J. Frisch, Combining quantum mechanics methods with molecular mechanics methods in ONIOM, J. Chem. Theory Comput., 2 (2006) 815-826. 

This presentation is structured in the following way. The first section outlines the procedure for the quantum mechanics and classical mechanics approach. The following two sections contain an overview of how to establish a density functional theory and molecular mechanics method along with the theoretical background for... 

K. Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM, 7. Chem. Theory Comput. 2006,2, 815-826. 

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-... 

Nevertheless, as with any theory or technique there are certain limitations with this method that should be understood. The users of the molecular mechanics method must be careful about extending these methodologies beyond... 

Combined quantum mechanical/molecular mechanical methods are not, of course, restricted to studies of reactions but can also be used to study association processes and conformational transitions. Most implementations use a two-zone model as described above, but Morokuma and colleagues have described a multilayered approach called ONIOM [Svensson et al. 1996]. ONIOM is a particularly apt name given that a typical calculation is constructed from a series of layers For example, a three-layer ONIOM calculation on the Diels-Alder reaction involved an inner core treated with the B3LYP density functional approach, the intermediate layer with a Hartree-Fock level of theory and the outer layer with MM3. A particular feature of ONIOM and its related methods is that they provide rigorous gradients and second derivatives, so enabling properties such as vibrational frequencies to be calculated [Dapprich et al. 1999]... 

Another related computational approach to ligand discovery is the method of database mining. Here, the HTS approach is essentially carried out in-silico. Libraries of small molecules are converted to three-dimensional structures using molecular mechanics methods incorporated into programs such as CONCORD and GORINA.These three-dimensional libraries of small molecules can. in theory, contain almost infinite numbers of potential ligands. In practice, it is convenient to consider compounds that are already (commercially) available. The Available Chemicals Database (ACD), - for example, contains some 260,000 compounds and is frequently used as the basis for database mining trials. 

In this chapter, we study small-molecule conformations and energetics using different levels of theory (molecular mechanics force field, semiempirical, and QM) to reproduce conformations found in the CSD. While our eventual goal is to predict the actual crystal form, here we focus on the conformation of the small molecule, with only one example to show the use of an accurate conformation to be used in the prediction of the solid form. We study two particular interaction types that tend to be poorly reproduced with standard force fields close intramolecular S--0 interactions and halogen X O interactions however, the methods presented here are generalizable to other interactions. We study two heavily used small-molecule force fields, the MMFFs variant of MMFF [38, 39] and the OPLS 2005 version of OPLS [16, 40], and demonstrate how modifications to the latter can improve the generation of structures with low RMSD relative to small-molecule crystal structures. 

Higashi M, Truhiar DG (2008) Electrostatically embedded multiconfiguration molecular mechanics based on the combined density functional and molecular mechanical method. J Chem Theory Comput 4 790-803... 

K. Aidas, K. V. Mikkelsen and J. Kongsted, Modelling Spectroscopic Properties of Large Molecular Systems. The Combined Density Functional Theory/Molecular Mechanics Approach , J. Comput. Methods Sci. Eng., 2007, 7, 135. 

Theory and implementation of calculation of spin-spin couplings within combined quantum mechanics/molecular mechanics methods have been applied by Mogelhoj et for prediction of spin-spin couplings in liquid water and acetylene in aqueous solution. They have also discussed the role of a solvent on spin-spin couplings across hydrogen bonds in the water dimer. 

Gresh N, Andres Cisneros G, Darden TA, Piquemal J-P (2007) Anisotropic, polarizable molecular mechanics studies of inter- and intramolecular interactions and ligand-macromolecule-complexes. A bottom-up strategy. J Chem Theory Comput 3 1960-1986 Field MJ, Bash PA, Kearplus M (1990) A combined quantum mechanical and molecular mechanical potential for moleeular dynamic simulations J Comput Chem 11 700-733 Kaminski GA, Jorgensen WL (1998) A quantum meehanieal and molecular mechanical method based on emla eharges applications to solvent effeets on organic equilibria and reactions. J Phys Chem B 102 1787-1796... 

Abstract It is well known that solvents can modify the frequency and intensity of the solute spectral bands, the thermodynamics and kinetics of chemical reactions, the strength of molecular interactions or the fate of solute excited states. The theoretical study of solvent effects is quite complicated since the presence of the solvent introduces additional difficulties with respect to the smdy of analogous problems in gas phase. The mean field approximation (MFA) is used for many of the most employed solvent effect theories as it permits to reduce the computational cost associated to the smdy of processes in solution. In this chapter we revise the performance of ASEP/MD, a quanmm mechanics/molecular mechanics method developed in our laboratory that makes use of this approximation. It permits to combine state of the art calculations of the solute electron distribution with a detailed, microscopic, description of the solvent. As examples of application of the method we smdy solvent effects on the absorption spectra of some molecules involved in photoisomerization processes of biological systems. 

Wang B, Truhlar DG (2010) Combined quantum mechanical and molecular mechanical methods for calculating potential energy surfaces tuned and balanced redistributed-charge algorithm. J Chem Theory Comput 6 359-369... 

Much of the information comes from computations. Ab initio theory produces useful results already at the Hartree-Fock level, and only in rare cases are there qualitative differences when electron correlation is introduced. Molecular mechanics methods such as MM3 do very well in a qualitative and even semiquantitative sense. 

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