Molecular Dynamics Simulation Of The Interactions Between Dendrimers And Biomembranes

In this thesis,we used All-atomic Molecular Dynamics(AA MD)to study the interaction between the Dendrimer and the membrane.Dendrimer is a new type of biomedical polymer materials.Dendrimer is composed of a central nucleus,repeating units and terminal functional groups.Due to its unique tree structure,it has broad application prospects in drug delivery,gene therapy and so on.There is a basic problem to make clear the drug carrier to span the cell membrane,that is,how the drug carrier complex enters into the cell.In the first part of this paper,we first constructed the Ambe03 all atom force field for the dendrimers,and studied the interaction between the third to fifth generation dendrimer and the membrane.Under the condition of the non-protonated state,dendrimer had little effect on the membrane,which could only be adsorbed on the surface of the membrane,and the membrane itself almost did not cause the disturbance.With the deepening of the degree of protonated state,the interaction becomes more and more intense.Under the acidic condition,dendrimer can be embedded in the middle of the membrane to a certain degree,which has a great influence on the configuration of the membrane,but the integrity of the membrane is not destroyed.In the second part,first of all,while appling external electric field,the possibility of increased under the condition of neutral dendrimer penetrates the cell membrane.Under high electric field,each generation dendrimer can penetrate the membrane,and membrane produced greater damage.Under low the electric field condition,only the fifth generation of the dendrimer penetrates into the phospholipid membrane.It can be explained that a new type of particle can be constructed by selecting relatively high generation of dendrimer with low electric field.Next,a double layer membrane system with internal and external ions concentration difference was constructed.We found that a high concentration of dendrimer can spanning the membrane.Finally use a graphite plate to division water environmental of the monolayer membrane system,we found that the dendrimers can be combined with RNA penetrate the cell membrane.