Protein force fields target data

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... 

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. 

Diversity of protein structure and function is enhanced by the different chemical functional groups seen in the 20 common amino acids. This variety, however, complicates the development of empirical force field parameters for proteins. For simplicity we will simply list a number of the model compounds used for the different amino acids. This is presented in Table 1. The selection of appropriate model compounds is based on a balance between the size of the compound and the available target data. For example, a large number of gas and condensed phase data are available for methanol however, sole use of that compound for the sidechains of serine or threonine avoids accurate tests of parameters associated with the covalent connection of the sidechain to the backbone. This is overcome by the use of larger compounds such as ethanol and isopropanol. Increases in computational resources will allow for ab initio calculations on larger model compounds. However, as discussed in the previous section, care... 

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