Peptides/polypeptides force fields

In Section II,D,4 we mentioned that recent ab initio calculations of dipole derivatives for the peptide group in NMA have been used to calculate intensities of IR bands in (Gly) I (Cheam and Krimm, 1985). Such calculated intensities are shown in Fig. 7, and it can be seen that they reproduce the observed intensities quite well. This kind of agreement indicates that the force field is a very satisfactory one, since intensities are a sensitive function of the eigenvectors. While (Gly) I is the only polypeptide so far for which intensities have been calculated, it can be expected that this technique will be used in the future to provide additional information on polypeptide chain conformation. 

The IR intensity of a normal mode is, from Eq. (79), proportional to (3, /3Q)2. One approach would be to determine experimentally a set of bond moment (electro-optical) parameters from which the (3. /dQ) could be calculated (Person and Zerbi, 1982). For molecules with as low a symmetry as peptides this presents serious difficulties. Our approach has been to use Eq. (76), dii/dQ = 2. (dfi/dSi)Lia, to calculate the dfi/dSi from NMA by ab initio Hartree-Fock methods, and to use the Lia obtained from our empirical force field for the particular polypeptide. 

The refinement of an empirical force field for a macromolecule usually starts with the vibrational analysis of a smaller model system of known structure followed by a transfer of these force constants to the larger system, with possible subsequent force constant adjustments. In the case of the polypeptides, the preferred model system for the peptide group has been fra 5-N-methylacetamide (NMA), CH3CONHCH3. Synthetic polypeptides of known structure such as )9-sheet polyglycine (PG ), R = H, and a-helical and )8-sheet poly(L-alanine) (PLA), R = CH3, have served as basic examples of the polypeptide systems. 

The glycine and alanine dipeptide analogs (GDA and ADA) have recently garnered theoretical attention, because they are the two simplest models of a polypeptide. Molecular mechanical force fields designed to model proteins are often parameterized to reproduce, as well as possible, the geometries and relative energies of the various GDA and ADA conformers. Since few experimental data are available, one must rely on theoretical studies. To date, DFT calculations on peptides have been limited to GDA and ADA. ... 

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