The origin, stability, and contribution to the formation of noncovalent interactions, such as hydrogen bonds and π - π stacking, have been already widely discussed. However, there are few discussions about the relevance of these weak interactions in DNA performance. In this work, we seek to shed light on the effect of hydrogen bonds and π - π stacking interactions on the biological behavior of DNA through the description of these intermolecular forces in CpG island-like (GC-rich) chains. Furthermore, we made some comparisons with TATA box-like (TA-rich) chains in order to describe hydrogen bond and π - π stacking interactions as a function of the DNA sequence. For hydrogen bonds, we found that there is not a significant effect related to the number of base pairs. Whereas for π - π stacking interactions, the energy tended to decrease as the number of base pairs increased. We observed anticooperative effects for both hydrogen bonds and π - π stacking interactions. These results are in contrast with those of TATA box-like chains since cooperative and additive effects were found for both hydrogen bonds and π - π stacking, respectively. Based on the chemical hardness and density of states, we can conclude that proteins may interact easier with GC-rich chains. We conclude that regardless of the chain length, a protein could interact more easily with these genomics regions because the π - π stacking energies did not increase as a function of the number of base pairs, making, for the first time, a first approximation of the influence of noncovalent interaction on DNA behavior. We did all this work by means of DFT framework included in the DMol3 code (M06-L/DNP). Graphical Abstract Cartoon representation of how nocovalent interactions affect the interaction of DNA with a protein, i.e., how hydrogen bond and π - π stacking interactions influence the biological behavior of DNA.
Keywords: Cooperativity; DFT; DNA; Hydrogen bonds; Promoter regions; π − π stacking.