The association of dehydro-epiandrosterone and adenosine triphosphate acid: A DFT study of interactions between prototypic biologically active molecules

Abstract

DHEA (dehydro-epiandrosterone) is a neurosteroid whose synthesis inside the brain as well its critical role in brain development, ageing, or memory effects, were recently proved. ATP (adenosine triphosphate acid) is very important as a source of energy in the human organism. The feasibility of an association between ATP and DHEA, investigated here, can be taken as a useful design testing ground in the search for new drugs helping to restore their level. DFT calculations are used to test the association potential of DHEA and ATP. Depending on the initial choice of the method, basis set and starting conformation, a set of quantitative association energies is obtained, the values being in the range −20 to −30 kcal/mol. These results point to the conclusion that such an association should be possible in many instances, and should also be relatively stable against potential perturbations originating from the environment. We use this model as an opportunity for a methodological discussion aiming at the comparative use of two different approaches to assess their performance and physical meaning. The first one is based on plane-waves and pseudo-potentials (with the ABINIT code) while the second one rests on Gaussian-type calculations (with the GAMESS package). The plane-waves approach was chosen as an alternative affording the direct calculation of association energies without the need to apply the so-called basis set superposition error (BSSE) correction. Actually, given a molecular box and a selected energy cut-off, the isolated molecules and the association complex are treated using the same extended basis set. Molecular parameters (geometries, charges and energies) are discussed with respect to the mechanism of association.