Interactions between nucleic acid bases in hydrogen bonded and stacked configurations: The role of the molecular charge distribution

Abstract

AbstractSome aspects of the use of simplified formulas for the evaluation the interaction energy between two molecules is discussed. This energy is obtained as the sum of four terms: electrostatic, polarization, dispersion, and short‐range (exponentially decreasing) repulsion. The effect of using several approximations is considered (i) for representing the charge distributions of the isolated molecules (which determine the electrostatic and polarization terms), and (ii) for evaluating the short‐range repulsion term. The various charge distributions considered are semiempirical atomic net charges (Del Re + Pariser‐Parr), atomic charges and dipoles (CNDO) and corresponding “effective” atomic charges, and many‐centered multipole distributions obtained from ab initio SCF calculations (charges, dipoles, and quadrupoles located on the atoms and the middles of segments joining pairs of atoms, whether chemically bonded or not). As concerns the short‐range repulsion, the various procedures considered are a sum of atom‐atom terms, a sum of bond‐bond terms, and the use of anisotropic van der Waals radii for heteroatoms (oxygen and nitrogen). In all cases, the dispersion energy is obtained as a sum of atom‐atom terms (of the R−6 type). These various procedures are checked in the case of the interactions between nucleic acid bases, for two rather different kinds of configurations, namely, hydrogen bonded and stacked. This comparison reveals a rather complicated picture, namely the results got from the various levels of approximation of the molecular charge distribution lead to different degrees of agreement according to different situations, e.g., for guanine‐cytosine interactions, qualitative agreement is found between the various methods as concerns the relative order of stacked and hydrogen bonded situations, while agreement is much less satisfactory for adenine‐uracile interactions. One of the main conclusions is that a sufficiently sophisticated representation of the molecular charge distribution is required in order to get reliable results for all possible configurations of a complex. Such comparative studies should bring significant help as concerns the development of the reliable simplified procedures for evaluating intermolecular interaction energies.