B.1.4 Summary and Discussion

PARAM1 is a refined set of parameters for the CHARMM potential energy form that describes the molecular mechanics of systems containing the covalent structures found in biological molecules. While an effort has been made to include different model compounds and conformations to generalize these parameters, they are primarily based on simple amides and hydrocarbons and intended for use in protein simulations. For non-protein systems it would be advisable to verify the properties of the constituents using model compounds (such as sugars and nucleotides) before macromolecular simulations are attempted. The accuracy of the geometric and force constants presented in this set is difficult to estimate. For some parameters such as bond stretching constants isolated modes could easily be identified and the parameter set to an accuracy of five percent or better. Conversely, angle bending and dihedral constants could not always be associated with particular modes, and significant correlations between the various parameters were observed during fitting. Even where least squares fitting was possible, none of these force constants should be regarded as accurate to better than twenty per cent. One corollary of this interdependence is the danger in naively readjusting parameters without repeating the analysis of all of the various model systems affected.

Given the number and extent of the changes presented in this work, the question of how they will affect results naturally arises. It should be noted that almost all of the changes presented here will tend to make molecules more rigid than they were previously. This will have implications in both the accuracy of the dynamics algorithm at a given step size, and the magnitude of the expected fluctuations. The behavior of the peptide bonds should not be markedly changed since the net effect of the parameter change on their vibrational modes is small. The aliphatic sidechains and coupling of motions through angle and dihedral terms is expected to show more prominent effects.

References:

Dollish, Fately, and Bentley (1975) Characteristic Raman Frequencies of Organic Compounds Wiley and Sons, New York.

Gelin Ph. D. Thesis (Chapters 2 and 4, Tables 12 to 15)

Gelin and Karplus (1975) JACS 97: 6996

Snyder and Schachtscheider (1965) Spectrochimica Acta 21: 169-195

Varsanyi (1974) Assignments to Vibrational Spectra of 700 Benzene Derivatives Halsted Press, Budapest.

Vinogradov and Linell (1971) Hydrogen Bonding van Nostrand.

Warshel and Lifson (1970) J. Chem. Phys. 53: 582

Warshel, Levitt, and Lifson (1971) J. Mol. Spect. 33: 84