The Interaction Of Peptide Carrier With Biomembranes:A Molecular Dynamics Simulation Study

The study of the penetrating peptides(CPPs)as drug delivery carriers interacting with biomembranes via molecular dynamics simulation,has become a promising field and is of great significance for the application of CPPs in the medical field.In this paper,the processes of the polyarginine peptide(R8)interacting with the curved and planar membrane were studied to investigate the effect of the curvature of biomembranes on the transport of the R8.Simultaneously,we also investigated the effect of the charged properties of planar membrane on the transport of the R8 peptide.Based on the results,it was found that:R8 can not spontaneously penetrate the biomembranes without the application of electric field,because it is difficult for R8 to overcome the high energy barrier that produced by the interaction between R8 and biomembranes only through the non-bonded interactions.However,when introducing the external electric field,R8 could penetrate through the biomembranes at a certain threshold electric field within a short time scale.Furthermore,we also found that the electric field can shorten the penetration time in a dose-dependent manner.This might because(?)the external driving force on R8 became stronger along with the stronger electric field,which makes it easier for R8 to overcome the energy barrier and(?)the strong electric field can quickly form hydrophilic pore in the membranes,through which the R8 can penetrate and achieve the penetration activity.In this paper,the role of membrane curvature,external electric field and membrane charged property in the transportation of R8 carrier was investigated via CGMD simulation,and we gave a further analysis to these obtained results via center of mass(COM)distance,Coulomb potential energy,Lennard-Jones(L-J)potential energy,potential of mean force(PMF)etc.All these findings in this work shed light on the role of external electric field on the penetration of R8 carrier through membranes and also gave some insights into the effects of membrane curvature and charged properties on the transportation processes of the peptide carriers.