Theoretical Research Of Hydrogen Bond In Base Pairs Containing Oxidative Guanine

Oxidative bases in DNA can lead to aging,numerous diseases and cancers.Hydrogen bonds?H-Bonds?play an important role in the interaction between nucleic bases.Study on oxidative base has become the focus of attention.8-oxo-G and Fapy-G are the most common guanine oxidation products.We have investigated the H-Bonds in oxidative base pairs,which are the model molecules in this paper,and obtained the following research results:1.Choosing the quantum chemical methods to research and analysis the structure,energy and other properties of base pairs containing 8-oxo-G and Fapy-G.All geometry optimations and NBO analysis are performed by B3LYP/6-31+G*method.The energies are determined at MP2/aug-cc-pVDZ level with BSSE corrections.The HOMO and LUMO are viewed at HF/STO-3G level.Comparing canonical base monomer with oxidative base monomer,and G:C with oxidative base pairs to discuss the similarties and differences in structure,energy and other properties between them.The study indicates that when G is oxidized to 8-oxo-G,the partial charge of N7 and O6get more nagetive,which enhances their ability as H-Bond donor.The H-Bond complexes formed at region 1 are more stable,the regions 2 and 3 have similar properties.When G is oxidized to Fapy-G,the partial charge of N7,N9 and O6 get more nagetive,which enhances O6 atom's ability as H-Bond donor.NH…N is stronger than NH…O in the oxidative base pairs containing Fapy-G.In NH…N,the H-Bonds of donor N atom in six-membered ring are stronger them of donor N atom in NH₂ or open-ring.In two types of oxidiative base pairs,comparing with canonical bases,the partial charge of proton acceptors in H-Bond complexes increasing by 0.05 e averagely;the partial charges of proton donors have a decrease of 0.02 e.Comparing with base pairs in gas phase,water solvent have influence on the binding energy and the order of the binding energy have been changed.2.Taking high level quantum chemistry methods and polarization force as benchmark,we developed the evaluation of hydrogen bond energy model in situ for oxidative base pairs.H-Bond energy is the sum of electrostatic,vdW and secondary interactions among atoms formed H-Bond.In this paper,the base pairs containing 8-oxo-G are chose as model molecules.Comparing the results of MP2 method with H-Bond energy of base pairs from evaluation of hydrogen bond energy model in situ,AAD is 2.07 kcal/mol.The advantage of this model is that we can obtain the H-Bond energy by corresponding interactions when the configuration of this system is known.So evaluation of hydrogen bond energy model in situ is a great potential model to evaluate H-Bond energy in biological molecule systems.The research shows that:?1?The analysis of base pairs in this paper can provide reference for enzyme to recognize and remove the oxidative base.?2?The hydrogen bond energy model developed by this paper can be applied to evaluate the hydrogen bond energy in oxidative base pairs,and its accuracy can compare with that of the quantum chemistry method method.It also can apply to dynamic research the property of H-Bond of dynamic behavior in DNA macromolecule systems containing oxidative bases.