Peptides protein force fields

S. Gnanakaran and A. E. Garcia, Validation of an all-atom protein force field from dipeptides to larger peptides, J. Phys. Chem. B 107, 12555-12557 (2003). 

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... 

Table 2 Partial List of Peptides used in the Testing of Protein Force Fields...

Such limitations emphasize the need for alternate peptides for the testing of protein force field parameters. 

N is the number of point charges within the molecule and Sq is the dielectric permittivity of the vacuum. This form is used especially in force fields like AMBER and CHARMM for proteins. As already mentioned, Coulombic 1,4-non-bonded interactions interfere with 1,4-torsional potentials and are therefore scaled (e.g., by 1 1.2 in AMBER). Please be aware that Coulombic interactions, unlike the bonded contributions to the PEF presented above, are not limited to a single molecule. If the system under consideration contains more than one molecule (like a peptide in a box of water), non-bonded interactions have to be calculated between the molecules, too. This principle also holds for the non-bonded van der Waals interactions, which are discussed in Section 7.2.3.6. 

I lagler A T, E Huler and S Lifson 1977. Energy Functions for Peptides and Proteins. I. Derivation of a Consistent Force Field Including the Hydrogen Bond from Amide Crystals. Journal of the American Chemical Society 96 5319-5327. 

ChemSketch has some special-purpose building functions. The peptide builder creates a line structure from the protein sequence defined with the typical three-letter abbreviations. The carbohydrate builder creates a structure from a text string description of the molecule. The nucleic acid builder creates a structure from the typical one-letter abbreviations. There is a function to clean up the shape of the structure (i.e., make bond lengths equivalent). There is also a three-dimensional optimization routine, which uses a proprietary modification of the CHARMM force field. It is possible to set the molecule line drawing mode to obey the conventions of several different publishers. 

Jorgensen, W. L, Tirado-Rives, J. The OPES force field for proteins. Energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Soc. 1988, 110, 1557-1555. 

Before providing empirical examples of protein spectra and unfolding, it is useful to present some computational results that represent the state of the art in terms of theoretical analyses for the IR and VCD of idealized peptides. IR spectra had been theoretically computed using empirical force fields and idealized geometries for a number of years... 

Hagler, A.T., Huler, E., Lifson, S. Energy functions for peptides and proteins. 1. Derivation of a consistent force field including the hydrogen bond from amide crystals./. Am. Chem. Soc. 1974, 96, 5319-5327. 

Kaminski, G.A., Friesner, R.A., Tirado-Rives, J., Jorgensen, W.L. Evaluation and reparametriza-tion of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B 2001, 105, 6474-87. 

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