A 2ND GENERATION FORCE-FIELD FOR THE SIMULATION OF PROTEINS, NUCLEIC-ACIDS, AND ORGANIC-MOLECULES

We present the derivation of a new molecular mechanical force field fo r simulating the structures, conformational energies, and interaction energies of proteins, nucleic acids, and many related organic molecule s in condensed phases. This effective two-body force field is the succ essor to the Weiner et al, force field and was developed with some of the same philosophies, such as the use of a simple diagonal potential function and electrostatic potential fit atom centered charges. The ne ed for a 10-12 function for representing hydrogen bonds is no longer n ecessary due to the improved performance of the new charge model and n ew van der Waals parameters. These new charges are determined using a 6-31G basis set and restrained electrostatic potential (RESP) fitting and have been shown to reproduce interaction energies, free energies o f solvation, and conformational energies of simple small molecules to a good degree of accuracy. Furthermore, the new RESP charges exhibit l ess variability as a function of the molecular conformation used in th e charge determination. The new van der Waals parameters have been der ived from liquid simulations and include hydrogen parameters which tak e into account the effects of any geminal electronegative atoms. The b onded parameters developed by Weiner et al. were modified as necessary to reproduce experimental vibrational frequencies and structures. Mos t of the simple dihedral parameters have been retained from Weiner et. al., but a complex set of phi and psi parameters which do a good job of reproducing the energies of the low-energy conformations of glycyl and alanyl dipeptides has been developed for the peptide backbone.