The electrostatic potential fitting methods for the determination of atomic charges are applied to polypeptides on the basis of the fragment molecular orbital (FMO) method. We show that the charges determined in the pair-approximation stage agree with those determined from the conventional molecular orbital method within an error of 1%. Analyzing the dependency of charges on the structural variation of glycine trimer and the reproducibility of electrostatic potential on the surface of the ligand-binding pocket of estrogen receptor, we also show the applicability of the FMO method for atomic charge determination using the electrostatic potential fitting. (C) 2007 Elsevier B.V. All rights reserved.