Development of ABEEMσπ polarizable force field for oxidized adenine base pairs: investigation of the interaction and mutagenic mechanism

Hydrogen-bonding and stacking interactions play a unique role for structure and replication of DNA. When adenine in DNA is oxidized, it increases the number of hydrogen bond donor and acceptor sites, and may lead to various mutations. 8-oxo-A is the most common oxidative product of adenine. Taking high-level ab initio calculations as benchmarks, we developed the ABEEM σπ polarizable force field and investigated the charges, structures, energies and mutations of base pairs containing canonical bases and 8-oxo-A. During this process, we do a great deal of ab initio, ABEEM σπ and other force field calculations for investigation, testing and calibration. The results of this work show that the angle formed by two base planes is buckled in the oxidized base pairs, and 79 % of buckled angles are larger than 5.0°. Comparing the results of ab initio with those of ABEEM σπ , the linear correlation coefficients of the charges, dipole moments and interaction energies are 0.99, 0.96 and 0.96, respectively; the ABEEM σπ force field provides reliable information on hydrogen-bonding, stacking interactions and mutation processes. In the DNA double helix, the mutations of AT → GC, AT → TA or AT → CG would happen. Meanwhile, the active centers of nucleophilic or electrophilic reaction transfer during AT → GC, AT → TA and AT → CG mutations. The results also indicate that the performance of the ABEEM σπ polarizable force field is generally better than that of the common force fields, and its accuracy can compare with that of the MP2 method. These studies supply a solid basis for further investigations of dynamical behavior of DNA fragments including oxidized adenine by the ABEEM σπ polarizable force field.