ABEEM/MM Polarizable Force Field Of Charged Phospholipids

Phospholipids are the key component of cell membranes.Lipid bilayers serve as the basic backbone of cell membranes and are involved in many life activities.Although a variety of membrane properties have been obtained experimentally,there are still many details of biochemical reactions,and dynamic changes that need to be simulated theoretically at the molecular level.In this thesis,five charged phospholipids,such as DOPG,DPPG,DMPG,DLPG and POPG,and PG-n H₂O are studied by developing the new ABEEM/MM polarizable force field parameters.The fluctuating charge potential functions of five phospholipids mentioned above are constructed according to ABEEM/MM model.The phospholipid headgroups is divided into five fragment molecules,such as DMP,MAS,PDO,GLYP and PG.The stable structures of negative and neutral fragment molecules are optimized at the MP2/6-31+G（d）and the MP2/6-31G（d）level,respectively.The force field parameters are iteratively optimized and finally determined to fit the QM results.The computational results of the ABEEM/MM are compared with the QM results,and the average absolute deviations（AADs）,root mean square deviations（RMSDs）,and relative root mean square deviations（RRMSDs）of bond lengths for the fragment molecules are below 0.025（?）,0.043（?）and 3.47%,respectively.The AADs,RMSDs,and RRMSDs of bond angles are below 4.88°,7.45°and 6.8%,respectively;The AADs,RMSDs,and RRMSDs of dihedral angles are below 7.77°,10.94°and 9.7%,respectively.In order to verify the reliability of the potential energy function constructed in this thesis and the transferability of the parameters.Based on fragment molecules,the determined parameters are applied to five phospholipids.The M06-2X/6-31++G（d,p）and the M06-2X/6-31G（d）are used to optimize the structures of the polar headgroup and hydrophobic tail groups,respectively.In comparison with the QM results,the AADs,RMSDs and RRMSDs of bond lengths for phospholipids are less than 4.7E^-4（?）and 0.043（?）,and 3.8%,respectively.the AADs,RMSDs and RRMSDs of bond angles are less than 2.27°,4.20°and 3.8%,respectively.the AADs,RMSDs and RRMSDs of dihedral angles are less than 1.58°,16.81°and 15.2%respectively.According to whether there can be charge transfer between phospholipids and water,the local and global conservation models of PG-n H₂O are constructed.The transferability of parameters is verified,and ABEEM/MM polarizable force field of lipids is constructed by calculating the charge distributions,energies and structures.The AADs and RRMSDs of hydrogen bond lengths obtained by the local conservation model and the global conservation model are 0.134（?）,9.0%and 0.108（?）,7.0%,respectively.The AADs and RRMSDs of hydrogen bond angles are 5.46°,4.2%and 9.26°,6.9%,respectively.The AADs and RRMSDs of binding energies are 7.90 kcal/mol,7.4%and 3.77 kcal/mol,3.4%,respectively.Compared with two models,the global conservation results are better,indicating that it is necessary to take account of charge transfer between phospholipids and water.The Mulliken charge distributions of the fragment molecules,phospholipids and PG-n H₂O are calculated at the HF/STO-3G level.The linear correlation coefficients of the ABEEM/MM charge distributions and QM results are all above 0.98.In conclusion,ABEEM/MM polarizable field of charged phospholipids developed in this thesis can accurately describe the structures,charge distributions and binding energies of phospholipids and PG-n H₂O.It provides an important reference for further construction of ABEEM/MM polarizable force field,which can be applied to simulate membrane proteins.