Study On The Structure And Properties Of Phospholipid Molecules Using ABEEMσπ/MM

Phospholipid molecules,as an important component of biomembranes,play an important role in many life activities.Because many molecular details in biomembranes are difficult to obtain in experiments,molecular dynamics simulation has become an important tool to obtain the structures and dynamic informations of biomembranes.Based on the results of the quantum chemical(QM)ab initio method,this paper applies and develops the atomic-bond electronegativity equilibrium floating charge molecular force field(ABEEMσπ/MM),to establish the polarizable force field of phospholipid molecules.The phospholipid molecules are parameterized hierarchically,and the parameters of the small molecules fragments representing the lipid functional groups are first optimized,and then they are applied to larger model compounds and phospholipids.The tetramethylammonium(TMA)ion and dimethyl phosphate(DMP)are used as model molecules of polar head group of the phospholipid,the methyl acetate(MAS)is used as a model molecule of esterified glycerol skeleton,and the short straight-chain alkane and olefins are used as model molecules of aliphatic hydrocarbon tail.The QM calculation was performed on the above model molecules to construct the ABEEMσπ/MM floating charge potential energy function of phospholipid molecules,related bond lengths,bond angles,dihedral angles,and charge parameters are determined The potential energy function is then applied to calculate the properties of the DPPC molecule such as structure,energy and charge distribution.Results show that the results obtained by ABEEMσπ/MM and QM are in good agreement.The average absolute deviation(AAD)of bond length,bond angle and dihedral angle are only 0.00001 ?,0.01°,0.01°,respectively,the relative root mean square deviation(RRMSD)are only 0.01%,0.01%,0.01%,respectively,and the linear correlation coefficient of charge distributions are 0.96.When the head group is combined with 1,2 and 3 water molecules,the root mean square deviation(RMSD)of the binding energy are 0.69,0.18 and 0.26,and the RRMSD are 4.65%,0.68%,1.14%,respectively.Furthermore,the structures,energies and charge distributions of five kinds of phospholipid molecules,DMPC,DLPC,POPC,DOPC and DOPE,are calculated and compared with QM results to test the reliability and transferability of force field parameters.The results show that the ABEEMσπ/MM results are in good agreement with those of QM.The RMSD of the dihedral angles are less than 0.01 ?,1.63°and 4.86°,respectively,and the RRMSDs are less than 1.14%,1.49% and 4.40%,respectively.The binding energy of the head group combined with 1~3 water molecules has an RMSD no more than 0.69 kcal/mol,RRMSD smaller than 4.65%,and the linear correlation coefficient of the charge distribution is greater than 0.96.