A computational characterization of the hydrogen-bonding and stacking interactions of hypoxanthine

Abstract

The hydrogen-bonding and stacking interactions of hypoxanthine, a potential universal nucleobase, were calculated using a variety of methodologies (CCSD(T), MP2, B3LYP, PWB6K, AMBER). All methods predict that the hydrogen-bonding interaction in the hypoxanthine-cytosine pair is approximately 25 kJ mol(-1) stronger than that in the other dimers. Although the calculations support suggestions from experiments that hypoxanthine preferentially binds with cytosine, the trend in the calculated hydrogen-bond strengths for the remaining natural nucleobases do not show a strong correlation with the experimentally predicted binding preferences. However, our calculations suggest that the stacking interactions of hypoxanthine are similar in magnitude to the hydrogen-bonding interactions at all levels of theory (with the exception of B3LYP, which incorrectly predicts stacked dimers to be unstable). Therefore, stacking interactions should also be considered when analyzing the stability of DNA helices containing hypoxanthine and the use of larger models that account for both hydrogen-bonding and stacking within DNA duplexes will likely result in better agreement with experimental observations. For the majority of the dimers, PWB6K and AMBER provide reasonable binding strengths at reduced computational costs, and therefore will be useful techniques for considering larger models.

Comparison of Intrinsic Stacking Energies of Ten Unique Dinucleotide Steps in A-RNA and B-DNA Duplexes. Can We Determine Correct Order of Stability by Quantum-Chemical Calculations?

“…The d-polarization functions are capable of filling the gap between the interacting monomers, which significantly improves the description of base stacking interactions compared with the standard 6-31G* basis set. The MP2/6-31G*(0.25) method has been the most widely used ab initio technique to study aromatic stacking in the past literature 31,35,50,51,60,85,100,101,[107][108][109][110][111][112][113][114][115][116][117][118][119][120] and has only recently been replaced by CBS(T). The MP2/6-31G*(0.25) method is entirely sufficient to capture the nature of base stacking, and therefore all conclusions reported with this method remain qualitatively valid.…”

Experimental and theoretical rationalization for the base pairing abilities of inosine, guanosine, adenosine, and their corresponding 8‐oxo‐7,8‐dihydropurine, and 8‐bromopurine analogues within A‐form duplexes of RNA

“…Overall, it is important to note that the model does not take into consideration stacking interactions and other conformational changes, thus limiting the amount of information that can be drawn from this data, which is in agreement with other models. [ 58 ] However, it does provide an important picture in some cases and also yielded good evidence for the proposed base pairs. We established base pairing trends for all the possible combinations of the modifications, lesions, and canonical nucleobases described herein.…”

Theoretical insights into the nature of intermolecular interactions in cytosine dimer

“…However, the exchange, dispersion and induction contributions also play an important role [7]. So far, the attention has been mainly focused on the calculations of the total stabilization energies of NAB complexes [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. It is well established that dispersion component is the main source of stabilization of stacked nucleic acid bases.…”