An ab initio distributed multipole study of the electrostatic potential around an undecapeptide cyclosporin derivative and a comparison with point charge electrostatic models

An SCF calculation has been performed on C₆₃H₁₁₃N₁₁O₁₂, a derivative of the immuno‐suppressive drug cyclosporin, using a 3‐21G basis set and a Direct SCF method. A distributed multipole analysis has been performed on the resulting charge density to give a set of multipoles at each atomic site, which are used to calculate the electrostatic potential around the molecule. The potential maxima and minima on the accessible surface of the molecule are compared with those predicted using the corresponding Mulliken charges, and also using a potential‐derived point‐charge model based on the force‐field of Kollman et al. The Mulliken charges give a misleading picture of the electrostatic potential around this peptide. The potential‐derived charges give results which are in far better agreement with the ab initio distributed multipole model, despite being derived from calculations on smaller molecules with different basis sets and geometries. The limitations of point‐charge models for describing the electrostatic interactions of polypeptides are discussed.