PubMed2006
Parametrization and testing of a new all-atom force field for organic molecules and peptides with fixed bond lengths and bond angles are described. The van der Waals parameters for both the organic molecules and the peptides were taken from J. Phys. Chem. B 2003, 107, 7143 and J. Phys. Chem. B 2004, 108, 12181. First, the values of the 1-4 nonbonded and electrostatic scale factors appropriate to the new force field were determined by computing the conformational energies of six model molecules, namely, ethanol, ethylamine, propanol, propylamine, 1,2-ethanediol, and 1,3-propanediol with different values of these factors. The partial atomic charges of these molecules were obtained by fitting to the electrostatic potentials calculated with the HF/6-31G quantum-mechanical method. Two different charge models (single- and multiple-conformation-derived) were also considered. We demonstrated that the charge model has a stronger effect on the conformational energies than the 1-4 scaling. The choice of a charge model affected the conformational energies of even the smallest molecules considered, whereas the effect of the 1-4 electrostatic or nonbonded scaling was apparent only for 1,3-propanediol. The best agreement with high-level ab initio data was obtained with the multiple-conformation-derived charges and with no scaling of the 1-4 nonbonded or electrostatic interactions (scale factors of 1.0). Next, the torsional parameters of a large number of neutral and charged organic molecules, assumed to be models of the side chains of the 20 naturally occurring amino acids, were computed by fitting to rotational energy profiles obtained from ab initio MP2/6-31G calculations. The quality of the fits was high with average errors for torsional profiles of less than 0.2 kcal/mol. To derive the torsional parameters for the peptide backbone, the partial atomic charges of the 20 neutral and charged amino acids were obtained by fitting to the electrostatic potentials of terminally blocked amino acids using the HF/6-31G quantum-mechanical method. Then, the phi-psi energy maps of Ac-Ala-NMe and Ac-Gly-NMe were computed using MP2/6-31G//HF/6-31G quantum-mechanical methods. The phi-psi energy map of Ac-Ala-NMe was used for refinement of the nonbonded parameters for the backbone nitrogen and hydrogen bonded to it. Subsequently, the main-chain torsional parameters were obtained by fitting the molecular mechanics energies to the phi-psi energy maps of Ac-Ala-NMe and Ac-Gly-NMe. The transferability of the entire force field was demonstrated by reproducing the main energy minima of terminally blocked Ala3 from the literature. The performance of the force field was also evaluated by simulating crystal structures of small peptides. By comparison of simulated and experimental data, examination of the torsional-angle and atom-positional root-mean-square deviations of the energy-minimized crystal structures from the corresponding X-ray model structures demonstrated high accuracy of the force field.