Development Of ABEEMσπ Polarizable Force Field For Systems Base Pairs And Amino Acid Residues

Currently,exploring the microscopic mechanism of repairing DNA with repair enzyme is the research hotspots.In this paper,high level quantum chemistry method is used to calculate the interaction between bases or base pairs and amino acid residues.On the basis of this,the ABEEMσπpolarization force field,which is suitable for those systems is developed.The achievements are as follows:1.ABEEMσπpolarization force field and fiting parametersIn order to reasonably describe the hydrogen bond interaction between base pairs and amino acid residues,this paper redefines partial atomic labels of oxidized guanine,and fits charge parametersχ*,η*and k _HB through a regression and least-squares method.The dihedral angle and improper dihedral angle parameters after readjust keeps the base plane level successfully.Finally,the simulation results of ABEEMσπPFF are close to the real biomolecular system.2.Study on the interaction between bases and amino acid residues by quantum chemistryThose atoms forming hydrogen bonds in these structures containing Cys are not in the same plane,and the electronegativity of sulfur is small,and the range interacted with bases is small.The interaction in complexes containing Cys is the weakest,and the average hydrogen bond energy is 7.18 kcal/mol.Those same atoms in these structures containing Ser are in the same plane,but the interaction range is small.The interaction range in the structure containing Asn is large.Hydrogen bond energies of these two types of structures（10.81kcal/mol and 15.21 kcal/mol in average）are larger than those of structures containing Cys.Affected by electrostatic interaction,hydrogen bond energies of the structures containing charged side chain Arg（26.55 kcal/mol in average）are larger than those of uncharged structures obviously.Compared with monomer,those charges of acceptors become negative0.0419e in average,and those charges of hydrogen atoms become positive 0.0241e in average.3.Application of ABEEMσπpolarization force field in the interaction system between base pairs and amino acid residuesDue to ABEEMσπPFF not only explicitly gives the position and the partial charge of lone-pair electrons,but also introduces a function k _HB to fit special electrostatic interaction in hydrogen bond interaction regions,it can accurately simulate the polarization effect and charge transfer of hydrogen bond interaction,and the geometry and hydrogen bond structure of the system are maintained well.ABEEMσπPFF can accurately simulate the binding energy between base pairs and amino acid residues,which is induced by charge transfer.However the results of FFF are close to a straight line,and the AAD of AMBER OL15 even reached7.75 kcal/mol,which is about 30%of average energy from QM.For charged and sulfur-containing systems,the relative positions of the amino acid residue optimized by OPLS/AA and AMBER OL15 have changed significantly,and the original hydrogen bonds are broken.As well as a larger rotation of methyl and bending of the plane of base pair occurred in FFF.4.Study on the effect of aqueous solution on the system between 8-oxo-G:C and amino acid residues by quantum chemistryThe hydrogen bond interaction is weakened by aqueous solution.Compared with gas phase,hydrogen bond strength between base pairs and amino acid side chains in charged complexes has been decreased by 60%in average,and 12%in uncharged complexes.The charge variation of forming hydrogen bond sites under aqueous solution is about 10 times as much as that under gas phase.The second-order stabilization energy between base pairs and the amino acid residues in three body complexes is lower than that in isolated base pairs,which is 4 kcal/mol in gas phase,and 2 kcal/mol in aqueous solution.