The effect of basis set and electron correlation on the predicted electrostatic interactions of peptides

Abstract

The realism of molecular modelling studies of peptides depends on the model of the electrostatic forces, and thus on the quality of the wave function used to derive the atomic charges or multipoles. To establish this dependence, we have studied the electrostatic properties of N-acetylalanine Wmethylamide (CH3CONHCHCH3CONHCH3) calculated from a distributed multipole representation of both SCF and correlated wave functions with a range of respectable basis sets. The electron correlation is included in the wave function at second-order Maller-Plesset theory using a 'direct" method which calculates the relaxed electron density. To predict the electrostatic potential on the water-accessible surface of the peptide to within a few kJ mol-' requires a correlated wave function and a large basis set of double-zeta plus polarization quality or better. For a given basis set, the SCF wave function overestimates the electrostatic potential by around 15%, the inclusion of electron correlation producing a consistent change in the electron density. Changing the basis set, within a given ab initio method, also produces significant differences in the electrostatic potential around the peptide and in its electrostatic interaction with water. However, it is observed that the electrostatic potential for this peptide correlates strongly with the total dipole moment of the charge density, as the direction of the dipole moment is almost independent of basis set within each ab initio method. Upon correlating the wave function there is a small, almost constant, change in the direction of the dipole moment of 3.5O * 0.1O. Thus, the electrostatic potential calculated from smaller (split valence) basis sets can be scaled to give good agreement with more accurate calculations.

What happens to formamide during C—N bond rotation? Atomic and molecular energetics and molecular reactivity as a function of internal rotation

“…See the appendix in ref. 13 dicted to be 22.560 kcal/mol above the planar conformation and is not along the reaction coordinate.…”

Molecular Packing and Molecular Dynamics Study of the Transferability of a Generalized Nitramine Intermolecular Potential to Non-Nitramine Crystals

“…13 All of the above theoretical calculations were done using the basis set 6-3IG** (split-valence plus d-type and p-type polarization functions). 14 It has been previously shown 1516 that the neglect of electron correlation in self-consistent wave functions results in an overestimation of the electrostatic interactions and that this overestimate is mainly a scaling effect A scaling factor of 0.9 was shown to give improved agreement between the calculated and the experimental dipole moments for a set of eight small molecules, 15 in a study of the electrostatic interactions of a dipeptide, 16 and in determining the crystal structures of polar organic molecules. 17 Our previous study of the nitramine crystals 4 showed that the use of the 0.9 scaling factor for the electrostatic charges determined at the HF level significantly improves the accuracy of the predicted lattice energies of the crystals.…”

A Transferable Intermolecular Potential for Nitramine Crystals

“…Cox and Williams [25] have suggested that a scaling factor of 0.9 can be used to improve agreement between the calculated and experimental values of the dipole moments for a set of eight small molecules. The same factor has been justified in a study of the electrostatic interactions of a dipeptide [26], as well as in a more recent work related to the role of electrostatic interactions in determining the crystal structures of polar organic molecules [10].…”

“…It has been shown previously [25,26] that the neglect of electron correlation in self-consistent wave functions overestimates the electrostatic interactions; however, this is mainly a scaling effect. Cox and Williams [25] have suggested that a scaling factor of 0.9 can be used to improve agreement between the calculated and experimental values of the dipole moments for a set of eight small molecules.…”