Calculation of molecular geometries, relative conformational energies, dipole moments, and molecular electrostatic potential fitted charges of small organic molecules of biochemical interest by density functional theory

Abstract Density functional theory is tested on a large ensemble of model compounds containing a wide variety of functional groups to understand better its ability to reproduce experimental molecular geometries, relative conformational energies, and dipole moments. We find that gradient‐corrected density functional methods with triple‐ζ plus polarization basis sets reproduce geometries well. Most bonds tend to be approximately 0.015 Å longer than the experimental results. Bond angles are very well reproduced and most often fall within a degree of experiment. Torsions are, on average, within 4 degrees of the experimental values. For relative conformational energies, comparisons with Hartree‐Fock calculations and correlated conventional ab initio methods indicate that gradient‐corrected density functionals easily surpass the Hartree‐Fock approximation and give results which are nearly as accurate as MP2 calculations. For the 35 comparisons of conformational energies for which experimental data was available, the root mean square (rms) deviation for gradient‐corrected functionals was approximately 0.5 kcal mol −1 . Without gradient corrections, the rms deviation is 0.8 kcal mol −1 , which is even less accurate than the Hartree‐Fock calculations. Calculations with extended basis sets and with gradient corrections incorporated into the self‐consistent procedure generate dipole moments with an rms deviation of 5%. Dipole moments from local density functional calculations, with more modest basis sets, can be scaled down to achieve roughly the same accuracy. In this study, all density functional geometries were generated by local density functional self‐consistent calculations with gradient corrections added in a perturbative fashion. Such an approach generates results that are almost identical to the self‐consistent gradient‐corrected calculations, which require significantly more computer time. Timings on scalar and vector architectures indicate that, for moderately sized systems, our density functional implementation requires only slightly less computer resources than established Hartree‐Fock programs. However, our density functional calculations scale much better and are significantly faster than their MP2 counterparts, whose results they approach. © 1995 John Wiley & Sons, Inc.