Development Of ABEEM?? Polarizable Force Field To Explore The Water-mediated Indentify Machanism Of Oxidized Guanine By Repair Enzyme

The identification mechanism of oxidative damage has always been a research hotspot.Water plays an important role in the identification process,but the specific role is still unclear.Nowadays,the most widely used method for investigating the properties of biological macromolecular systems is force field.However,there is currently no suitable force field that can truly describe the electrostatic interactions and hydrogen bond in the complex system of the repair enzyme and oxidized base.This paper develops the ABEEM?? polarization force field for the composite system of oxidized base and repair enzyme in biological environment,then explores the mechanism of water-mediated mediation of oxidative guanine oxidation by the repair enzyme.The specific work is as follows:1.Development of ABEEM?? polarization field for composite systems of oxidized bases and repair enzymesIn order to realistically simulate the double helix structure of DNA in biological environment,based on the ABEEM?? polarization force field,the dihedral angle of the DNA backbone and the related parameters of the phosphorus atom in the phosphate group were refitted to consistent with those of ab initio calculations.Using the developed polarization force field,four DNA molecules were simulated.The relative displacement and structural parameters of the simulated system were compared with these of other force field results.The dihedral ?,?,?,and ? dihedral angles are closer to the experimental values than those of AMBER force field.The other structural parameters of these two force fields are similar.2.Investigate the role of water in identification guanine oxidation by ABEEM?? polarization force fieldThe repair enzyme and oxidized DNA complex were simulated by ABEEM??polarization force field in biological environment,both water molecule presence and absence between glutamine and oxidized guanine in the initial structure.These results all indicate that during the recognition process,the amino acid residue Gln always recognizes oxidized guanine through hydrogen bonds mediated by two water molecules.One water molecule is mainly media,and the other is assisted.During the identification process,there is an exchange phenomenon of water molecules.After a group of water is completed,the next group of water will be pulled to participate in the reaction and continue to identify oxidized guanine withamino acids.Radial distribution function and dwell time proved the correctness of the conclusion.3.Application fixed charge force field to simulate DNA oxidation in biological environmentThe molecular dynamics simulations of repair enzymes and oxidized DNA were performed using AMBER and ABEEM?? fixed charge force fields,respectively.The simulation results also show that the repair enzyme recognizes oxidative guanine must be mediated by water molecules,but the residence time of water molecules is too long by fixed charge force field,compared to that of polarization force field relative to the real.This also fully proves that the polarized force field is more suitable than the fixed charge force field to simulate the complex system of amino acids and oxidized bases,and is more suitable for discussion the repair mechanism of oxidized base.The above studies indicate that ABEEM?? polarization force field developed in this paper is suitable for the oxidized DNA and amino acid complex system under water environment.It is necessary for water molecules to participate in the recognize process between repair enzyme and oxidized guanine.We hope these result can provide further theoretical basis for drug research in this field.