Energetic Force Fields

In contrast to the methods mentioned above which differentiated between primary and secondary structure or utilized a data base of known protein structures, there is the possibility of utilizing one of the many potential energy functions which have been shown to accurately reproduce many features of proteins, including thermodynamics and molecular motions. The potential energy force fields vary in specific details, mainly depending on the target molecule for which they were developed. A very typical energy force field is shown below. 

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To account for barriers of rotation about chemical bonds, i.e., the energetics of twisting the 1,4-atoms attached to the bonds formed by the atoms 2-3, a three-term torsion energy function like that in Eq. (24) is used, in the given form or slightly modified, in almost every force field. 

Inadequate availability of experimental data can considerably inhibit the development of improved energy functions for more accurate simulations of energetic, structural, and spectroscopic properties. This has led to the development of class II force fields such as CFF and the Merck Molecular Force Field (MMFF), which are both based primarily on quantum mechanical calculations of the energy surface. The purpose of MMFF, which has been developed by Thomas Halgren at Merck and Co., is to be able to handle all functional groups of interest in pharmaceutical design. 

Many of the molecular modelling force fields in use today for molecular systems can be interpreted in terms of a relatively simple four-component picture of the intra- and inter-molecular forces within the system. Energetic penalties are associated with the deviation of bonds and angles away from their reference or equilibrium values, there is a function... 

Fig. 8. Stmctural representation of the energetic components of a typical molecular mechanics force field.

The second generation force fields for nucleic acids were designed to be used with an explicit solvent representation along with inclusion of the appropriate ions [28,29]. In addition, efforts were made to improve the representation of the conformational energetics of selected model compounds. Eor example, the availability of high level ab initio calculations on the conformational energetics of the model compound dimethylphosphate yielded... 

Jorgensen, W. L., Maxwell, D. S., Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 

Amadasi, A., Spyrakis, E., Cozzini, P., Abraham, D.)., Kellogg, G. E Mozzarelli, A. Mapping the energetics of water-protein and water-ligand interactions with the natural HINT force field predictive tools for characterizing the roles of water in biomolecules. J. Mol. Biol. 2006, 358, 289-309. 

Florian, J., Johnson, B. G., 1995, Structure, Energetics, and Force Fields of the Cychc Formamide Dimer MP2, Hartree-Fock, and Density Functional Study , J. Phys. Chem., 99, 5899. 

Piquemal J-P, Perera L, Cisneros GA, Ren P, Pedersen LG, Darden TA (2006) Towards accurate solvation dynamics of divalent cations in water using the polarizable Amoeba force field from energetics to structure. J Chem Phys 125 054511... 

Sefcik J, Demiralp E, Cagin T, Goddard WA (2002) Dynamic charge equilibration-morse stretch force field application to energetics of pure silica zeolites. J Comput Chem 23(16) 1507-1514... 

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