Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides

We present results of improving the OPLS-AA force field for peptides by mea ns of refitting the key Fourier torsional coefficients. The fitting techniq ue combines using accurate ab initio data as the target, choosing an effici ent fitting subspace of the whole potential-energy surface, and determining weights for each of the fitting points based on magnitudes of the potentia l-energy gradient. The average energy RMS deviation from the LMP2/cc-pVTZ(- f)//HF/6-31G** data is reduced by ca. 40% from 0.81 to 0.47 kcal/mol as a r esult of the fitting for the electrostatically uncharged dipeptides, Transf erability of the parameters is demonstrated by using the same alanine dipep tide-fitted backbone torsional parameters for all of the other dipeptides ( with the appropriate side-chain refitting) and the alanine tetrapeptide. Pa rameters of nonbonded interactions have also been refitted for the sulfur-c ontaining dipeptides (cysteine and methionine), and the validity of the new Coulombic charges and the van der Waals sigma 's and epsilon 's is proved through reproducing gas-phase energies of complex formation heats of vapori zation and densities of pure model liquids. Moreover, a novel approach to f itting torsional parameters for electrostatically charged molecular systems has been presented and successfully tested on five dipeptides with charged side chains.