The Proton Transfer Mechanism Of GC Base Pair

As one of the most basic biological material, deoxyribonucleic acid (DNA) is the important material of genetic information and the material basis for the genetic process. Based on complementary base-pairing, DNA molecule form stable structures. The binding of two bases occurs through hydrogen bonds, which result in any change and reaction of hydrogen bonds in base pair may affect the accurate transmission of information. The hydrogen-bonded proton-transfer reaction in the base pairs are systematically studied here using density functional methods to understand the mechanism of proton transfer and their effects to the geometric structures and properties of DNA molecular. These works provide important theoretical basis for studying diseases, which are caused by DNA tautomerism and genetic mutations, and their detection. The main contents can be stated as follows:The single proton transfer of fourteen protonated base pairs (GC+H)+are studied using B3LYP/DZP++method. The conventional protonated structures, transition state and proton-transferred product structures of every relevant species are optimized in the gas phase. PCM single-point energies at the gas phase optimized structures are computed to analyze the influences of aqueous solution. Each transition state and proton-transferred product structure has been compared with the corresponding conventional protonated structure to conclude that charge distribution plays a decisive role in hydrogen-bonded proton transfer pathway, in addition, the hydrogen-bond length also plays a role in proton transfer pathway. The structure with significant twist arising from proton transfer might cause DNA damage.The double proton transfer of five guanine-cytosine base pairs after hydrogen atom addition with lowest energies are studied using B3LYP/DZP++method. The conventional protonated structures, and the corresponding transition state and proton-transferred product structures in the stepwise and concerted mechanisms are optimized in the gas phase. PCM single-point energies at the gas phase optimized structures are computed to analyze the influences of aqueous solution. The study demonstrate that the double proton transfer reaction is more favorable than the single proton transfer reaction, and the concerted mechanism has an energetic advantage of the stepwise mechanism in the gas phase, while the stepwise mechanism becoming more favorable in water. Solvent effects is conducive to single proton transfer, but increase double proton transfer reaction energy.The proton transfer reaction in DNA trimers with four sequences are studied here using ONIOM(M06-2X/6-31G*:PM3) methods. The single GC base pair and the corresponding transition state and proton-transferred product structures are fully optimized using M06-2X/6-31G*method. The DNA trimers and the corresponding transition state and proton-transferred product structures are fully optimized using ONIOM method. All the structures are optimized in gas phase and in aqueous solution. The computational results demonstrate that the electrostatic interaction between the peripheral base pairs and the middle base pair has important effects on proton transfer in gas phase, while this interaction is greatly shielded in aqueous solution, which lead to proton transfer pathways and energy profiles of four DNA trimers with different sequences have the same tendency.The proton transfer reaction in DNA trimers, which the most stable hydrogenated GC base pair neutral, cation, and anion are embodied in, with four sequences are studied here using ONIOM(M06-2X/6-31G*:PM3) methods. The single GC base pair neutral (H*addition to the C8of guanine), cation (H+addition to the N7of guanine) and anion (H-addition to the C6of cytosine), and the corresponding transition state and proton-transferred product structures are fully optimized using M06-2X/6-31G*method. The DNA trimers and the corresponding transition state and proton-transferred product structures are fully optimized using ONIOM method. All the structures are optimized in gas phase and in aqueous solution with the same methods to consider the solvent effect. The computational results reveal that the structures with dATGCAT and dGCGCGC sequence facilitate proton H4a transfer, but hinder proton H1transfer, and the structures with dCGGCCG and dTAGCTA sequence facilitate proton H1transfer. Anions are more easy to take place proton-transfer reaction than neutrals and cations, and all the proton transfer reactions in anions are exothermic.