A fast method for calculating geometry-dependent net atomic charges for polypeptides

A new method for calculating geometry-dependent atomic charges (GDACs) for polypeptides is presented. It overcomes the limitations of the partial equa lization of orbital electronegativity (PEOE) and modified PEOE (MPEOE) meth ods, which depend only on connectivity, not geometry. Introduction of dista nce-dependent damping factors helps to include the effect of environment in determining the variation of bond distance (without explicit contribution of the correlated variation of bond angles), and thereby to reduce the numb er of parameters required to represent different atomic species. Since the correlation between the geometry and the dipole moments of molecules is cru cial for this method, ab initio molecular orbital calculations were carried out to obtain the geometries and dipole moments with the 6-31G** basis set at the level of B3LYP theory. When bond distances are fixed prior to a cha rge calculation, the methodology outlined here leads to a direct calculatio n of the permanent molecular charge distribution represented as a set of di stributed monopoles that depend on the geometry of the molecule. Hence, thi s method automatically accounts for the transferability of charges of small amino acid residues to build up a large polypeptide molecule, and can ther efore provide an approximate description of any redistribution of charge de nsity of large polypeptide molecules. The parameters characterizing the cha rge transfer in the formation of bonds were optimized by using dipole momen t components and total dipole moments of 50 molecules that serve as models for the backbone and side chains of proteins. The calculated total dipole m oments of these 50 molecules agree well with the ab initio results within a n error of 5%. The new charge scheme has been applied to seven conformers o f N ' -acetylalanine-N ' -methylamide (Ac-Ala-NHMe) with good agreement bet ween ab initio and GDAC dipole moments. This method, however, gives poor re sults for conjugated systems that are larger than amides.