Theoretical Study Of The Damaged Nucleic Acid Base Pairs

There are enormous bases in the nucleic acid, which is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. Nucleobases are heterocyclic aromatic organic compounds containing nitrogen atoms. There are various interactions between the bases, and the hydrogen bonding interaction is very important to the structure and property of nucleic acid. In this study, the hydrogen bonding interaction between the nucleic acid bases were investigated by quantum chemistry MP2 method. The effect of oxidation on the stability of G:C and A:T base pairs and the pairing properties of the damaged bases were studied by supermolecular method.The character and essence of the hydrogen bonds between the bases were analyzed systematicly. The main results are as follows:1. The DNA bases A, C, G, T and 19 oxidized bases were optimized at MP2/6-31G** level and characterized as minimum by frequency analysis. Subsequently the Natural Bond Orbital (NBO) analysis was performed starting from the optimized geometries. The difference between the normal bases (A, C, G, T) and the oxidized bases were analyzed by the geometry parameters, the atom charge and bond orbitals. The results indicate that some of the damaged bases, such as fapy-A, fapy-G, 5-OH-6H-T, 6-OH-5H-T, T-glycol, C-glycol, U-glycol and Iso-acid, show the nonplanar structures, and the'maximum distance of the atom deviate from the base plane'was used to indicate the noplanarity of the damaged bases.2. The hydrogen bonds between 19 oxidized bases and four normal bases (A, C, G, T) were studied by supermolecule method at MP2/6-31G** and MP2/6-311++G** levels, the effect of oxidation on the configuration and strength of Watson crick base pairs G:C and A:T were discussed. The pairing properties of the damaged bases were studied by comparing the hydrogen bonding strength between the damaged bases and the normal bases. The Natural Bond Orbital (NBO) and Atoms in molecules theory (AIM) analysis were performed to compare the pairing ability to nucleic acid bases. The results indicate that base pair 2-OH-A:T increase the binding energy of A:T by 25%, while the base pairs 5-OH-U:G, 5,6-OH-U:G, Iso-acid:G, U-glycol:G and xanthosine:C decrease the binding energy of G:C by 39%,40%,44%,42% and 53%, and the ratio of binding energy change of the rest pairs are within 6%. Moreover, the results show that the favorable mispairing bases are 5-OH-C,5-OH-U, U-glycol,8-oxo-G, xanthosine, 8-oxo-A, fapy-A, and subsequently cause to the gene mutation of CG→GC,CG→TA, CG→TA, GC→TA, GC→CG, AT→CG,AT→GC.3. The hydrogen bonds between the damaged U bases (DHU and s4U) and RNA bases (A, C, G, U) were studied by supermolecule method. The binding energies, NBO analysis and AIM analysis were performed, and the results show that they form the most binding energy pairs with base G.4. To investigate the relationship between the interaction energy and geometry parameters, we have calculated the dependence of interaction energy on the buckle angle and the distance between the hydrogen bond donor and acceptor between bases. Furthermore, the relation between the electron density and distance, and the relation between the E(2) and distance were discussed in detail.The MP2 method of M?ller–Plesset perturbation theory is suitable in the studied systems, which gives an approving calculation accuracy and efficiency. Moreover, the three parameters'ratio of binding energy change','ratio of distance change','ratio of dihedral angle change', were proposed to compare the stability of damaged base pairs in nucleic acid, the results are similar to the reported experimental results and these can be useful for the nucleic acid study and gene mutation research.