The Coarse-graining Of Poly(ethylene Oxide) And Poly(propylene Oxide) Homopolymers And Poloxamers In Big Multipole Water (BMW) And MARTINI Force Field

Using computer simulation technology to study the physical and chemical processes that occur on the surface of cell membranes is an important aspect of studying the complex phase behavior of biological systems.Because water molecules play a very important role in these physical and chemical processes,selecting a suitable water model in computer simulations to describe the properties of the cell membrane surface in the aqueous environment accurately for studying the complex phase behavior of cell membrane surfaces and the specificity interaction of biological macromolecules and cell membrane surfaces plays a decisive role.Until now,many water models have been developed to describe the structure and thermodynamic properties of water phases at different simulation scales.The BMW(Big Multipole Water)water model has three charge sites can reproduces the dipole moment and quadrupole moment tensor of 4-water clusters in atomistic simulations.In addition,the BMW water model has good compatibility with the MARTINI force field describing phospholipid membrane system composed of phospholipid molecules,so it is often used to study the complex physical chemistry of biological systems such as the specific interactions between biological Poloxamer copolymers and phospholipid membrane surfaces effect.Poloxamer copolymer consists of poly(ethylene oxide)(PEO)blocks and poly(propylene oxide)(PPO)blocks,with a wide range of applications in drug delivery and improving the properties of pharmaceutical formulations.In view of this,in this paper,we built a coarse-grained model of PEO/PPO homopolymer and Poloxamer copolymer based on the BMW-MARTINI force field framework,and determined the effective interaction between coarse-grained particles through a large number of all-atom and coarse-grained molecular dynamics simulations,which provides a reliable theoretical framework for future research on the complex phase behavior of the Poloxamer copolymerphospholipid membrane composite system.The main research contents of this paper include: 1)Optimizing the force field parameters of the BMW water model,so that the model can better describe the thermodynamic,structural and dynamic properties in BMW environment;2)Based on the coarse-grained rules of the MARTINI force field,we develop a coarse-grained model of the PEO/PPO homopolymer and the corresponding Poloxamer copolymer;3)Fitting the effective bonded interaction parameters between the coarse-grained particles,which makes the distributions of bond length,angle,and dihedral of the PEO/PPO homopolymer and Poloxamer copolymer consistent with those from the all-atomic molecular dynamics simulation;4)Adjusting the nonbonded interaction parameters between coarse-grained particles allows the corresponding coarse-grained model to accurately describe the conformational behavior of PEO/PPO homopolymers and Poloxamer copolymers in a dilute solution environment and the homopolymer hydrophilic/hydrophobic properties.