Interaction Of LL-37 Antimicrobial Fragments And Membrane By Molecular Dynamic Simulations

Antimicrobial peptides are a small class of host defense proteins. It can protect plants, animals and other multicellular organisms from infection. LL-37 is the only Cathelicidin antimicrobial peptide in the human body, which is very important in antibacterial, anti-virus, anti-tumor and immune regulation and so on. Although LL-37 has been studied, the molecular mechanism and process of LL-37 play an active role in the process of antibacterial activity need to be further studied. Studying on the interaction of LL-37 and cell membrane for the understanding of the cellular toxicity mechanism of LL-37 and its antibacterial mechanism is important. Experimental research is an important aspect of understanding the process and mechanism of this process. However, due to the limitations of time and space resolution, at present, it is not yet available at the atomic level to provide specific information on the interaction process of antimicrobial peptide LL-37 with the cell membrane. Molecular dynamics simulation has become a research on biological molecules and their complexes of a kind of indispensable important tool, in the field of biological macromolecules and their interaction has made a series of important results, but also a rapid development. Molecular dynamics simulation method can simulate the evolution of a molecular system in the four-dimensional spacetime, provide conformation with the information of the time change, and then get the simulation system structure, dynamic and thermodynamic processes. It is the effective supplement of experimental study. Therefore, molecular dynamics simulations can provide us an important tool to study the antibacterial mechanism of antimicrobial peptides from the micro level.In this paper, the molecular dynamics simulation method was used to study the interaction between the antimicrobial peptides and membrane of simulated mammal and simulated bacteria. We choose GROMOS 53A6 force field and SPC water model to simulate the conventional molecular dynamics simulation. Firstly, the structure characteristics of antimicrobial peptides in different membrane environments were studied. Second, the interaction of antimicrobial peptides with different membranes was studied. Finally, the characteristics of the membrane are analyzed. Molecular dynamics simulation can reveal the micro mechanism of the interaction between antimicrobial peptides and different membranes at the molecular level. It increase the understanding of the process of this kind of action. The following are the main results of the study1. Structural characteristics of antimicrobial peptides in different membrane environments. The antibacterial activity of the antibacterial peptide was related to the change of the secondary structure(helix). Simulation trajectory analysis found that the interaction of antimicrobial peptides and the bacterial membrane can maintain a partial helical structure. While it with the mammalian membrane, there is no helical structure. It showed that the helical structure of antimicrobial peptides could be closely related to its antibacterial activity.2. Interaction of antimicrobial peptides with different membranes. The number of hydrogen bonds formed during the interaction with the bacterial membrane was increased in comparison with the role of the mammalian membrane. The distance between the center of mass of the peptide and the membrane is close. These features also show that the antimicrobial effect of antimicrobial peptides is relationship with the characteristics of the membrane.3. Changes in membrane associated with antimicrobial peptides. The interaction of antimicrobial peptide segment FK-13 with the bacterial membrane is more than that of the mammalian membrane. It is more close to the center of mass of the membrane and cause the membrane to a large disturbance. Thus, the membrane has a destructive effect on the membrane.This paper is divided into five chapters. The first chapter is the introduction. It mainly introduced antimicrobial peptides, the interaction of antimicrobial peptides and different types of membranes and research progress. It includes the function of antimicrobial peptide LL-37 in human immune system, as well as the associated diseases. In the second chapter, the basic theory of molecular dynamics simulation is introduced, which consisits of molecular dynamics simulation method, empirical force field, GROMACS software and molecular dynamics simulation in the application of antimicrobial peptides. The third chapter is the research object and method. It introduces the choice of the simulation object, the simulation of the membrane equilibrium and the simulation of the peptide membrane system. The fourth chapter is the study result and analysis. Firstly, the paper introduces the simulation convergence, then from the structure characteristics of the peptides, peptides and membrane interaction, membrane structure characteristics of three aspects analysis of the antimicrobial peptides with different membrane interactions. The fifth chapter is the summary and prospect. It summarized the main conclusions of this work, innovation and existing problems. We hope that this work is helpful to designd low toxic, efficient antibacterial agents in the future.