DETERMINATION OF NET ATOMIC CHARGES USING A MODIFIED PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY METHOD .1. APPLICATION TO NEUTRAL MOLECULES AS MODELS FOR POLYPEPTIDES

Modified methods for the determination of net atomic charges, based on an existing scheme utilizing the partial equalization of orbital electronegativity method, are proposed. The new methods introduce (as constraints) experimental dipole and, where possible, quadrupole moments of a set of molecules chosen to resemble the different atomic environments found in proteins. As a consequence, the atomic charges reproduce accurately the experimental values of molecular dipole and quadrupole moments. The electrostatic potential surface, calculated with the new net atomic charge set, compares well to a surface obtained from a moderate level ab initio calculation (6-31G**). However, it is observed that the new charges are of twice the magnitude of those obtained from investigations in which the charges are determined from a least-squares fit to the calculated ab initio electrostatic potential (potential-derived method). The methodology outlined leads to a direct calculation of the permanent molecular charge distribution represented as a set of distributed monopoles, dependent only on the connectivity of the molecule. Hence, the method circumvents assumptions concerning the transferability of charges and can therefore approximately describe any redistribution of charge density upon assembly of amino acid residues to form a polypeptide. It is envisioned that the method introduced here will be of use in providing an approximate representation of molecular charge distributions in extended systems, specifically large polypeptide molecules. © 1990 American Chemical Society.