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

Abstract

Some 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.

Intermolecular interactions: Elaboration on an additive procedure including an explicit charge‐transfer contribution

“…This is consistent with the results on the water dimers and with preceding studies devoted to such interactions [21,27]. …”

“…Concerning the base pairs, table V shows that in the present procedure the Hoogsteen A-T base pair has a greater stability than the Watson-Crick base pair, in agreement with previous theoretical results [26,27]. Our optimal interaction energy -13.7 kcal/mol, is close to the complexation enthalpy of -13 kcal/mol [28] determined in vacuo by field ionization mass spectrometric techniques.…”

Molecular mechanical studies of d(CGTACG)2: complex of triostin A with the middle A - T base pairs in either Hoogsteen or Watson-Crick pairing.

“…However, a few years after the Watson-Crick (WC) structure was solved, the discovery of an alternative base-pairing scheme by Hoogsteen (2) threw some doubt on the basic WC model, particularly for DNA containing adenine and thymine bases. This doubt is further enhanced by the results of theoretical calculations (3,4), which suggest that Hoogsteen (HG) base pairing for isolated adenine and thymine bases [involving hydrogen bonding between the N7 of adenine and the N3 hydrogen of thymine (N7 ... H-N3) and between the C6 amino group of adenine and the C4 oxygen of thymine (N6-H ... 04)] is as favorable or slightly more favorable than WC [involving hydrogen bonding between the N1 of adenine and the N3 hydrogen of thymine (N1 ... H-N3) and between the C6 amino group of adenine and the C4 oxygen of thymine (N6-H ... 04)]. Furthermore, -molecular mechanical and structural studies on adenosine suggest that the syn conformation of the adenine ring (5) relative to the sugar (required for HG hydrogen bonding) is of comparable stability to the anti conformation found in the WC structure.…”

Analysis of pair interaction in a bipolar mesogen 4‐(4‐hydroxylbutyloxy)‐4′‐cyano‐biphenyl: A comparative study based on semiempirical and DFT methods

“…where R As a further refinement [19], the dependence of the repulsion term on the residual charge has been taken into account by multiplying it by two factors, which are functions of the charges on the two atoms concerned. Thus, if q k and q m are the net charges and the atomic number N k and N m the actual electron population are (N k À q k ) and (N m À q m ) and atom-atom repulsion term [20] is E rep (k, m).…”