Molecular mechanics approaches

Bakowies, D., Thiel, W. Hybrid models for combined quantum mechanical and molecular mechanical approaches. J. Phys. Chem. 100 (1996) 10580-10594. 

In an attempt to aid interpretation of the IR spectrum of MbCO we decided to model the full protein by use of a hybrid quantum mechanics/molecular mechanics approach (QM/MM), to evaluate changes in the CO stretching frequency for different protein conformations. The QM/MM method used [44] combines a first-principles description of the active center with a force-field treatment (using the CHARMM force field) of the rest of the protein. The QM-MM boundary is modeled by use of link atoms (four in the heme vinyl and propionate substituents and one on the His64 residue). Our QM region will include the CO ligand, the porphyrin, and the axial imidazole (Fig. 3.13). The vinyl and propionate porphyrin substituents were not included, because we had previously found they did not affect the properties of the Fe-ligand bonds (Section 3.3.1). It was, on the other hand, crucial to include the imidazole of the proximal His (directly bonded to the... 

Jorgensen et al. [49] developed a combined quantum mechanical and molecular mechanical approach for study of organic reactions and applied it with success to many solution reactions. Inspired by this Kollman et al. [50, 51] developed the approach further for study of enzyme reactions. This quantum mechanical/free energy (QM/... 

A. V. Bochenkova, M. A. Suhm, A. A. Granovsky, and A. V. Nemukhin, Hybrid diatomics in molecules based quantum mechanical/molecular mechanical approach applied to the modeling of structures and spectra of mixed molecular clusters Ar (HCl)m and Ar (HF)m. /. Chem. Phys. 120, 3732 3743 (2004). 

Our protocol and the adiabatic mapping procedure described by Ha et al (8) have two features in common. They are both based on molecular mechanics approach, and they both start with several structures scattered at regular intervals over the (( ), j ) space. But the objectives of the approaches are fundamentally different. Whereas the adiabatic mapping procedure is intended to fully characterize the conformational energy surface of disaccharides, our... 

Over the last 10 years, all these severe limitations of the traditional molecular mechanics approach have been tackled. The appropriate use of molecular mechanics, molecular dynamics, quantum mechanics and computer graphics has given in a number of cases useful qualitative data on solvation and binding, with good agreement between theory and experiment (Kollman and Merz, 1990). 

Another way of performing calculations using the cluster model is the use of a hybrid method. It is a theoretical method, which uses different approaches for different parts of the molecular system. The ONIOM method is one of the hybrid methods developed quite recently to facilitate accurate ab initio calculations of large chemical species. The ONIOM method (n-layered integrated molecular orbital and molecular mechanics approach) [29] is a multi-level extrapolation method, in which the studied molecular system is divided into two or more parts or layers. The most important part of the system from the chemical point of view (the inner part, IP) is treated at a high" level of theory (the HL method - a high level of ab initio molecular orbital method) and the rest of the system is described by a computationally less demanding method (the LL method - the lowest ab initio approximation or even semiempirical or molecular mechanic approximations) [30]. 

P. Sherwood. Hybrid quantum mechanics/molecular mechanics approaches, In J. Grotendorst, Modern Methods and Algorithms of Quantum Chemistry, Proceedings (2 ed.), NIC Series, 3, John von Neumann Institute for Computing, Jtilich, 285, 2000. 

An unrestrained molecular-mechanics approach was used for PtC and PtK, and the resulting models were evaluated on the basis of energy, chemical shifts, coupling constants, and a small number of NOE cross-peaks [72] [114], An important conclusion of the PtC modeling study was that only a combination of conformers from both the LL and NP families explained all the experimental NMR data, while the PtK study concluded that the data was best fit by two models in the LL family (see below). An approach based solely on NOESY data was used for PtW and PtL [73] [77], resulting in one... 

The repulsion energies in various o-di-f-butyl heterocycles 85-88 were calculated using a simplified molecular mechanics approach (69T453) (Scheme 67). Here again, the importance of ring geometry is clear. 

Ridder L, AJ Mulholland (2003) Modeling biotransformation reactions by combined quantum mechanical/molecular mechanical approaches From structure to activity. Curr. Topics Med. Chem. 

The performance of the cluster approach can be improved dramatically if it is combined with the recently developed ONIOM methodology43 which is an n-layered integrated molecular orbital and molecular mechanics approach. A threelayered version of the ONIOM approximation allows a quantum-mechanical study of systems which are normally considered with molecular mechanics methods to be performed. The three-layered total energy expression for the ONIOM scheme is defined as... 

An alternative to the molecular mechanical approach is the quantum mechanics (QM) framework. Much of work has been devoted in the past decades to establish and improve QM methodologies ranging from simple semiempirical methods to high-level correlated ab initio methods [20,21,29], The substantial advantage of quantum mechanical calculations is the inclusion of all n-body effects, including charge transfer and polarisation. Furthermore, bonds are automatically formed and broken as necessary along the simulation. 

This section provides the fundamental equations for the quantum mechanical and molecular mechanical approach for determining the energies of molecules interacting with a structured environment. We can illustrate the QM/MM procedure as indicated in Figure 13-1 for a system where one part is described by quantum mechanics (QM) and the other part is described by classical mechanics or molecular mechanics (MM). The electrons and the nuclei of the QM system are treated separately at positions r7 and Rm, respectively. We represent the particles in the MM part by effective charges positioned at the atomic sites, Rs, and induced dipole moments located at (R ). 

This section contains the background for the combination of density functional theory and molecular mechanics. Following the basic philosophy of quantum mechan-ics/molecular mechanics approaches we partition the total system into at least two parts which can be treated simultaneously. The quantum mechanical subsystem is described using DFT and the classical subsystem is given by molecular mechanics. Based on the QM/MM approach we have that the total energy of the system is... 

The well known Irving-Williams series1253 2561 and the HSAB principle1257-1 are established empirical concepts related to the stability of metal complexes, and the question of whether these are accounted for in a general molecular mechanics approach have not always been appreciated when metal ion selectivities have been modeled via empirical force field calculations. The assumption that the position of the minima and the steepnesses of the potential energy functions for the metal-ligand bonds for varying metal ions and constant donor sets accurately reflect var-... 

K. Aidas, K.V. Mikkelsen, J. Kongsted, Modelling spectroscopic properties of large molecular systems, the combined density functional theory/molecular mechanics approach, J. Chem. Meth. Sci. Eng. 7 (2007) 135. 

Mercer IP, Abend S, Gould IR, Klug DR. A quantum mechanical/molecular mechanical approach to solvation dynamics tested by three pulse photon echo measurements. In Elsaesser T, Fujimoto JG, Wiersma DA, Zinth W, eds. Ultrafast Phenomena, Berlin Springer-Verlag, 1998 532-534. 

In Fig. 1 we show the correlation between E and experimental heats of formation for the (complete) set of C22H14 benzenoid isomers. For comparison we also present some recent data for the same set of compounds, obtained by a semiempirical MNDO method [21] and by the MMX/PI version of molecular mechanics calculations [22], The only conclusion we wish to draw from Fig. 1 is that HMO theory is capable of reproducing the experimental enthalpies of benzenoid hydrocarbons with an accuracy which is not much worse than that of the much more sophisticated (and highly parametrized) molecular orbital and molecular mechanics approaches. 

Although few applications of these very recently implemented models have yet appeared, some calculations for free energies of transfer into aqueous solution are available.Polarization of the solute has been analyzed by reference to the molecular dipole moment,including comparison to a hybrid quantum mechanics/molecular mechanics approach,and the effect of aqueous solvation on conformational equilibria and simple nucleophilic reactions has been examined.] jo consideration of CDS solvation terms in conjunction with these models has appeared. 

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