A TRANSFERABLE DISTRIBUTED MULTIPOLE MODEL FOR THE ELECTROSTATIC INTERACTIONS OF PEPTIDES AND AMIDES

The accurate representation of the electrostatic potential around a molecule requires not only point charges at each atom, as generally assumed in molecular modeling studies, but also point dipoles, quadruples, etc., to represent the nonsphericity of the atomic charge distribution within the molecule. Such distributed multipole models have been obtained for several amides and several dipeptides with hydrocarbon side chains by a distributed multipole analysis (DMA) of their ab initio SCF wave functions, calculated with a 3-21G basis set. The atomic multipole moments appear to be reasonably transferable to other molecules provided that at least the directly bonded functional groups are the same. This makes it possible to build distributed multipole models to be used for calculating electrostatic interaction energies for polypeptide molecules without requiring an ab initio calculation on the entire molecule, either by using average atomic multipole moments or by transferring the DMAs of peptide fragments. Both schemes are tested in various applications, including the electrostatic potential around an alanine dipeptide in various conformations, and around an undecapeptide cyclosporin derivative. The results show that transferable distributed multipole models enable the electrostatic interactions of polypeptides to be modeled at a new level of accuracy. The main limitations are the errors inherent in any transferable electrostatic model that does not explicitly represent polarization effects. © 1990, American Chemical Society. All rights reserved.