Other force fields

In this section we briefly outline the explicit form of several general purpose force fields and present the results of calculations on amino and nitro compounds performed as part of their validation. 

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These numbers are not negligible. At present such effects are on the average compensated by other force field terms through empirical parametrization. 

An atom that has sp hybridization tends to be coplanar with its attached atoms. This effect is accounted for by improper torsions in other force fields and by out-of-plane-bending interactions in... 

In computational chemistry it can be very useful to have a generic model that you can apply to any situation. Even if less accurate, such a computational tool is very useful for comparing results between molecules and certainly lowers the level of pain in using a model from one that almost always fails. The MM+ force field is meant to apply to general organic chemistry more than the other force fields of HyperChem, which really focus on proteins and nucleic acids. HyperChem includes a default scheme such that when MM+ fails to find a force constant (more generally, force field parameter), HyperChem substitutes a default value. This occurs universally with the periodic table so all conceivable molecules will allow computations. Whether or not the results of such a calculation are realistic can only be determined by close examination of the default parameters and the particular molecular situation. ... 

Significant progress in the optimization of VDW parameters was associated with the development of the OPLS force field [53]. In those efforts the approach of using Monte Carlo calculations on pure solvents to compute heats of vaporization and molecular volumes and then using that information to refine the VDW parameters was first developed and applied. Subsequently, developers of other force fields have used this same approach for optimization of biomolecular force fields [20,21]. Van der Waals parameters may also be optimized based on calculated heats of sublimation of crystals [68], as has been done for the optimization of some of the VDW parameters in the nucleic acid bases [18]. Alternative approaches to optimizing VDW parameters have been based primarily on the use of QM data. Quantum mechanical data contains detailed information on the electron distribution around a molecule, which, in principle, should be useful for the optimization of VDW... 

The MM3(2000) force field is the basis of this chapter. The program includes an induced dipole calculation that allows for the treatment of induction.69 This improvement in the electrostatics yields better predicted dipole moments than in previous versions of MM3. It should be pointed out that most other force fields use point charges whereas the MM series of programs is based on point dipoles. 

Several force fields have been used in molecular mechanics calculations of amino, nitro and nitroso compounds. The most intensive work has been done with MM2 and, in recent years, also with MM3, probably due to the generally recognized high performance of these force fields and since they are the only ones which have undergone extensive specific parameterization for these systems, however, several other calculations are also found in the literature (see below). We therefore start with the MM2 and MM3 force fields where we briefly outline the specific form of the potential functions and discuss, in some detail, the parameterization procedure for the type of compounds discussed in this chapter. We then turn to several other force fields which have not undergone specific parameterization but were nevertheless used in the calculations (AMBER, Tripos, DREI-DING, UFF). We conclude with a brief comparison of the energetic performance of all force fields. 

A-value. Both MM2 and MM3 do a good job in reproducing the A-value of the amino and dimethylamino groups. MM3 also faithfully reproduces the experimental A-value for the nitro group while MM2 slightly underestimates this number. None of the other force fields is consistent in reproducing the experimental results along the nitro, amino and A,A-dimethylamino series. 

Piperidine derivatives. Again, both MM2 and MM3 do a good job in reproducing the experimental axial-equatorial energy differences of piperidine derivatives. All other force fields rather seriously overestimate the stability of axial conformations and consequently underestimate the energy difference. The only exception is UFF, which overestimates the aforementioned energy difference for /V-rncthy I piperidine and 2-methylpiperidine. 

MOLECULAR BUILDER. One of the earliest successful MM programs by Boyd (37) has been used as a prototype of several other force field programs. For example, a modified version is in-... 

The importance of electrostatic effects in protein structure and function has long been recognized (Tanford and Kirkwood, 1957 Peratz, 1978 Warshel and Russell, 1984 Rogers, 1989). It is generally believed that electrostatic field effects are among the first that come into play when two protein molecules approach each other. The reason for this is that electrostatic fields reach much further out than any other force fields that we associate with protein-protein interaction. It is reasonable to expect that motion in the combined electrostatic field of both molecules helps to orient the molecules for subsequent docking. 

The program MacroModel contains many modified versions of other force fields, e.g., AMBER, MM2, MM3, OPLSA. ... 

There are several points that need to be kept in mind when developing a new force field or modifying an existing one. The most important is that any force field consists of a strongly correlated set of parameters. Thus, no force field parameter should be modified without testing how this influences all structural parameters and establishing whether other force field parameters need to be modified as a consequence of the change. To minimize the number of parameters that need to be developed or refined empirically, it is important to base as many as possible on reliable experimental data. 

For the determination of a compound s chemical exergy value we need to define a reference environment. This reference environment is a reflection of our natural environment, the earth, and consists of components of the atmosphere, the oceans, and the earth s crust. If, at P0 and T0, the substances present in the atmosphere, the oceans, and the upper part of the crust of our earth are allowed to react with each other to the most stable state, the Gibbs energy of this whole system will have decreased to a minimum value. We can then define the value of the Gibbs energy for a subsystem, the "reference environment"—at sea level, at rest, and without other force fields present than the gravity field—to be zero as well as for each of the phases present under these conditions. It is a logical extension of these assumptions to... 

Because of the empirical specification of its electronic interaction parameters molecular mechanics is routinely discounted as devoid of theoretical underpinning. This conclusion is certainly too harsh. Apart from connectivity, the electronic basis of all other force-field concepts has already been demonstrated ... 

Some quantity which will act as a measure of the magnitude of the body force acting on the flow. Consideration here will only be given to buoyancy forces, i.e., to forces arising dueio gravity. However, the method used here to derive a measure of this force can easily be applied when other force fields exist. 

In the functional form of other force fields additional terms, such as the cross terms are included. These terms couple internal coordinates, e.g. changes of planar angle are coupled with adjacent bonds stretching. Cross terms are important in many cases, e.g. for a better reproduction of vibrational spectra of molecules. 

However, it is important to exercise caution in comparison with other force-fields for similar molecules as was shown in the case of JV-methylacetamide [5], The differences in calculated force constants is the result of using different basis sets. It is noteworthy that the potential energy distributions are not greatly different in the tables for vapor and aqueous phase. This suggests that alteration of the force... 

These components include the forces exerted on the th particle by all the particles, the forces exerted by electromagnetic and other force fields, and the walls of the containing vessel. 

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