Force Fields MMFF

The MM2, MM3, and Merck (MMFF) force fields perform best for a wide range of organic molecules. 

This chapter describes the basis of molecular mechanics models and introduces the SYBYL and MMFF force fields. It also compares and contrasts molecular mechanics and quantum chemical models. 

The molecule preparation step includes also conformational expansion using a torsional search or a combined Monte Carlo Multiple Minimum/Low Mode search. During the search, the intramolecular hydrogen bonds are not considered. Molecules can be minimized, OPLS-2005 or MMFF force fields [86, 87] are available, and also two continuum solvation models (distance-dependent dielectric or GB/SA). A double criterion is used to eliminate redundant conformations it uses distances between pairs of corresponding atoms within a 1 kcal moh1 energy window. 

Cheng et al. [166] assigned the absolute configuration of the alkaloid (—)-linarinic acid (37) with the help of theoretical calculations. Via molecular mechanics, a conformational search was performed with the MMFF force field, using water... 

The structure of daphmanidin B (67), C25H36NO6, was elucidated by 2D NM R data to possess a l-azabicydo[5.2.2]undecane moiety, like daphnezomines F and G [46]. The relative stereochemistry was deduced from NOFSY correlations. The conformation of the unit (C-2-C-5, C-18 to C-2, C-19, and N) in the l-azabicyclo[5.2.2]undecane moiety, with a twist-chair form as shown in Figure 18.16, was consistent with the results of a conformational search using MMFF force field [60] implemented in the Macromodel program [59]. 

In addition to the classical force fields above, many other force fields have been developed for small drug molecules or macromolecules. The MM2, MM3, and MM4 force fields were developed by Norman L. Allinger for a broad range of chemicals, and CFF is a family of force fields adapted to a broad variety of organic compounds, polymers, metals, and so on. The MMFF force field was developed at Merck for a broad range of chemicals. ReaxFF is a reactive force field, developed by William Goddard and coworkers, is fast, transferable, and the computational method of choice for atomistic-scale dynamics simulations of chemical reactions. 

Figure 2 Calculated structures of conformations S (a) and SI with included Mg + (b) of cyclopeptide 8. The calculations were performed on the basis of the reported results by using MacSpartan 04 (Wavefunction, Inc.) and the MMFF force-field.

We first consider two model polypeptides an a-helix consisting of 15 alanine residues and an anti-parallel -sheet consisting of 17 glycine residues. Geometries of the polypeptides were obtained with the MMFF force field using the spartan... 

The CFF and MMFF force fields use charges calculated from the charge bond increments, as shown in equation (12)... 

Although least-squares based parameterization tools have been used for the derivation of the CFF, MM3/MM4, and MMFF force fields, improved methodology and software development is continuing. This will eliminate (or at least reduce) the need for human intervention in the parameterization process, and this will consequently speed the development of force fields for new functional groups and for all of the systems to which new force fields are being applied. Moreover, improvements in the accuracy of experimental measurements and quantum mechanical calculations are likely to continue for a long time, and the use of more fully automated parameterization tools will allow this new data, as well as new functional forms, to be rapidly incorporated into widely used force fields. 

For the relative energies, the OPLS-AA, MM3, and MMFF force fields were found to perform the best among the many alternatives. However, the last two force fields were not developed or tested in conjunction with simulations of condensed-phase systems. The MMFF force field was subsequently tested in Monte Carlo simulations of liquid butane, methanol, and A-methylacetamide (NMA). The computed densities and heats of vaporization for methanol and NMA were in error by ca. 25%, while butane did not stop expanding during the simulation at —0.5 °C. Poor results had previously been obtained for liquid butane with other force fields that had also not been developed in conjunction with fluid simulations. It is evident that computation of condensed-phase properties is necessary in the development of force fields for use in condensed-phase simulations. 

Mixed basis sets, 154 MM2, MM3, MM4 force fields, 40 MMFF force field, 40 MMP2, MMP3 method, 27 MNDO/d method, 89 MNDOC method, 87... 

To determine the AC of the enantiomers of 3, calculations were performed in the gas phase at 298 K for the arbitrarily chosen (5)-3. As a result of the high flexibility of the prenyl chain at C2, the initial steps of conformational search and geometry optimization were carried out for a fragment molecule (Figure 53.11). Conformational search was performed at the molecular mechanics level of theory employing MM+ and MMFF force fields. The conformers with relative energy (rel E.) within 6 kcal/mol of the lowest... 

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