Molecular Dynamics Simulation Of Microphase Separation Of Biomembrane And Its Interaction With Antibacterial Molecules

Cell is the smallest unit of life,and cell membrane is the most important component of a cell.Cell membrane(biomembrane)is normally composed of amphiphilic phospholipid molecules,cholesterols and proteins.This special membrane structure plays an important role in cell activity,such as signal transduction and substance transport.In a real biological system,the mechanism of action of cell membrane is complex and small both in time and space,so that the existing experimental techniques levels are difficult to determine the mechanism of action of the cell membrane.In recent years,with the development of computer science and the optimization of biological models,the computer simulation of biological systems has become a hot topic.This article mainly uses both atomistic and coarse grained molecular dynamics simulation methods to study the interaction between phospholipid membranes,peptides,antibacterial molecules and membrane proteins.The main resear-ch includes the following two aspects:1.Interactions among phospholipid membranes with antimicrobial peptides and antibacterial molecules.Studies included the changes in the structure of antimicrobial peptides in water and on the surface of phospholipid membranes,and antimicrobial peptides induce the formation of membrane pore with the help of membrane potential.Disturbance of the phospholipid tails by antibacterial molecules destroys the membrane structure.(a)The structural changes of the magainin antibacterial peptides and the CM 15 antibacterial peptides in different environments and the formation mechanism of membrane pores.With atomistic molecular dynamics simulations,we found that CM 15 antimicrobial peptides form two-by-two aggregates in water,and at the same time,they are twisted from the spiral structure to the folded structure.For magainin antimicrobial peptides,they tend to aggregate in both water environment and on membrane surfaces.Our simulations show that the magainin peptides show a disordered structure in the water,and when they meet at the surface of membrane,they firstly uncoil into a disordered structure and then convert to a folded structure.When an external electric field,which model the membrane potential,is applied to a single-membrane model,antimicrobial peptides can form pores more easily on the membrane surface.The greater electric field strength,the easier it is to form membrane pore.After the addition of ion pairs in the double-membrane model,the presence of-antimicrobial peptides increases transmembrane potential,so that antimicrobial peptides are more easily to form membrane pores.This results show that the cell environment and the structure of antimicrobial peptides play an important role in the formation of membrane pores.(b)How antibacterial molecules perturb the structure of phospholipid membranes.Using molecular dynamics simulation,we investigate that distinct structures of antibacterial molecules affect membrane in different ways.We considered the pyrrole dipyrrole and quaternized structures.Antimicrobial molecules are able to maintain stable structures in two forms at the center of the membrane:transmembrane structure,U-shaped structure.After the antibacterial molecules form a transmembrane structure,they affect the thickness of the phospholipid membrane.Antibacterial molecules with a chain length of 6 or 8 carbon atoms thin the membrane and reduce the degree of ordering of phospholipid tails,disrupting the membrane structure.Due to the positive charge of the nitrogen atom on the quaternized structure,antibacterial molecules also interact with the POPG phospholipid head group,affecting the phospholipid distribution.The simulation results can provide guidance for the design of antibacterial molecules in the future.2.Phospholipid membrane microphase separation.For this part we mainly study the phase separation mechanism of multi-component phospholipid membranes,and how the membrane proteins influence the microphase separation.The phase separation is found to be mainly controlled by phospholipid tails.When the degree of unsaturation of the lipid tails differs significantly,the phospholipid spontaneously separates the ordered microdomain formed by saturated phospholipids with cholesterol as well as the disordered microdomain formed by unsaturated phospholipids.We also fund that increasing the cholesterol concentration would promote the microphase separation take place as.When the length of the saturated phospholipid tail and the unsaturated phospholipid tail differ greatly,the antiregistered phase will be formed.However,if the difference is small,the registered phase will be formed.Since the ordered regions are packed closely and the disordered regions are arranged loosely,the membrane proteins tend to distribute in the disordered phase.The presence of membrane proteins sometimes affects the phase-separation behavior,e.g.,changing from antiregistered phase to registered phase.