Force field methods functional groups

Force fields split naturally into two main classes all-atom force fields and united atom force fields. In the former, each atom in the system is represented explicitly by potential functions. In the latter, hydrogens attached to heavy atoms (such as carbon) are removed. In their place single united (or extended) atom potentials are used. In this type of force field a CH2 group would appear as a single spherical atom. United atom sites have the advantage of greatly reducing the number of interaction sites in the molecule, but in certain cases can seriously limit the accuracy of the force field. United atom force fields are most usually required for the most computationally expensive tasks, such as the simulation of bulk liquid crystal phases via molecular dynamics or Monte Carlo methods (see Sect. 5.1). 

The picture of molecules being composed of structural units, functional groups , which behave similarly in different molecules forms the very basis of organic chemistry. The drawing of molecular structures where alphabetic letters represent atoms and lines represent bonds is used universally. Organic chemists often build ball and stick, or CPK space-filling, models of their molecules to examine their shapes Force, field methods are... 

Molecular modeling calculations (force-field methods, MMFF94s) at room temperature and NMR experiments have shown that the preferred orientation of the functional group [=N-N02] in 3 is in the trans-position the (Z)-isomer with lowest energy is more than 2.6 kcal mol above the optimal (F)-isomer [47]. Calculations as well as X-ray structure analysis have shown that the three C-N bonds involving atom C5 have some double bond character. The N-methyl group of 3 can flip easily from the anti- into the syn-position. The energies of its respective conformers, relative to the optional structure, are below 1.5 kcal mol . ... 

Equation (4-5) can be directly utilized in statistical mechanical Monte Carlo and molecular dynamics simulations by choosing an appropriate QM model, balancing computational efficiency and accuracy, and MM force fields for biomacromolecules and the solvent water. Our group has extensively explored various QM/MM methods using different quantum models, ranging from semiempirical methods to ab initio molecular orbital and valence bond theories to density functional theory, applied to a wide range of applications in chemistry and biology. Some of these studies have been discussed before and they are not emphasized in this article. We focus on developments that have not been often discussed. 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

A somewhat different approach has been implemented in MCSS (multiple copies simultaneous search) [10]. In this method, up to 5000 copies of a functional group are randomly distributed in the binding pocket and simultaneously minimized by a force field. The simultaneous optimization is performed in... 

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