Development Of ABEEMσπ Fluctuating Charge Polarizable Force Field For Oxidative DNA System In Liquid Phase

The accumulation of lots of oxidation bases can lead to biological aging,disease and even cancer.People concerned about the impact of oxidative base pairs on DNA,but there lacks of powerful research tools.Considering the problem of polarization and charge transfer in biological systems,we proposed a new model of charge conservation and developed a floating charge polarization force field which is suitable for studying of the properties of oxidative DNA in liquid phase in this paper.And we applied it to the research of DNA fragment-1ZFE.Details are as follows:1.Composite associated with charge conservation modelFor the complex system of deoxynucleotides and Na+ and(H2O)1～10,The average absolute deviation of charges on P,O1(P)and O2(P)from original ABEEM force field and HF/STO-3G level are 0.2177e,0.1906e and 0.1700e,which reflected a excessive polarization phenomenon.And it does not reflect the charge transfer phenomenon for Na+,whose charge is always-1e.The charge transfer from quantum chemical method occurs mainly in the parts of deoxynucleotide and Naa,transferring about 0.3e while transferring about Oe in the part of water which can be ignored.Accordingly,we proposed a new charge conservation model which combined with overall conservation and local conservation to calculate the charge distribution.2.charge calculationThe charge parameters of new force field based on the charge parameters of original force field.In the new force field charge parameters,we adjust the valence electronegativity and valence hardness of P,O1(P),O2(P)and Na+and added the electrostatic fitting function of Na+and lone pair electrons of O(W),Na+and lone pair electrons of O(P).We calculated the charge of four kinds of model molecules in liquid phase and gas phase by new force field and calculated linear correlation by comparing with the charge of HF/STO-3G level.The average absolute deviation of the charges of P,O1(P),O2(P)and Na+are 0.0200e,0.0570e,0.0718e and 0.0511e,the linear correlation coefficient of all kinds of systems above 0.96,the slope of the linear equation are close to 1.The new force field appropriately reflects the polarization effects and charge transfer phenomena.3.The planar structure of baseThere is a greater base plane bending after dynamic simulation of the system of base monomer in original force field,which is diffierent from the real biological system.For this,the parameters of torsions and the parameters of imports were refitted or added based on the parameters of original force field.Both the base plane in the system of base monomer and in the system of deoxynucleotide and Na+ can keep the smoothness of the base plane in liquid phase and gas phase.This is more in line with real biological system.4.The dymanic simulation of 1ZFEThe dymanic simulations of normal 1ZFE and oxidized 1ZFE in liquid phase and gas phase were performed.The simulation results show that the torsional amplitude of G increased and the stability between the base pairs weakened when G was oxidized to 8-oxoG.In liquid phase,the purine glycosidic angle of 8-oxoG was smaller then G of 5.81° and the bond length of three hydrogen bonds increased 0.4222A,0.3825 A and 0.5590 A,the bond angle of three hydrogen bonds decreases14.52°,15.15°and 24.57°.Gas phase has the same change trend.