Protein force fields model compounds

Protein force fields are necessarily complicated by the chemical nature of the amino acids comprising proteins. The chemical variability requires a wide number of model compounds be included during the parametrization process as target data. Furthermore, a significant number of test molecules should be selected these molecules should not be included with the model compounds in the original target data used in the optimization of the force field. This separation insures relatively unbiased testing of a force field to be performed. 

Proper parametrization of proteins requires the selection of appropriate model compounds for which adequate target data exist. As the peptide backbone C, O, N, H and C atoms are common to all amino acids selection of the appropriate model compounds for optimization of the peptide backbone parameters is central to the success of any protein force field. The most often used model compounds are NMA and ALAD, shown in Figure 1. Both structures contain the peptide bond capped by methyl groups. Earlier studies often employed formamide or acetamide as model compounds however, the free amino or aldehyde groups make them poor models for the peptide bond in proteins. Data available on NMA range from structural and vibrational data in both the gas and conden.sed pha.ses to crystal structures, pure solvent properties and heats... 

Vibrational spectroscopy has played a very important role in the development of potential functions for molecular mechanics studies of proteins. Force constants which appear in the energy expressions are heavily parameterized from infrared and Raman studies of small model compounds. One approach to the interpretation of vibrational spectra for biopolymers has been a harmonic analysis whereby spectra are fit by geometry and/or force constant changes. There are a number of reasons for developing other approaches. The consistent force field (CFF) type potentials used in computer simulations are meant to model the motions of the atoms over a large ranee of conformations and, implicitly temperatures, without reparameterization. It is also desirable to develop a formalism for interpreting vibrational spectra which takes into account the variation in the conformations of the chromophore and surroundings which occur due to thermal motions. 

The complete set of new parameters for the phosphate and phosphorothioate model compounds is given in Table II. The new atom type (SD) and parameters have been added to the AMBER 4.1 force field database for simulating proteins and nucleic acids. For completeness, we have also included a comparison of geometrical parameters taken from optimized model compound structures using the updated AMBER 4.1 force field and HF/6-31G basis set calculations. These values are given in Table III. 

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