Molecular Dynamics Simulation On The Orientation Of Single-helix Transmembrane Peptide In Membrane

Membrane proteins have a significant role in various life activities,such as respiration,nerve signal transdcuction,immune response and so on.There is an essential question during the membrane folding process still unresolved,the correct orientation of the transmembrane peptides,which is premise for peptides obtain biological fuctions.Therefore,a systematic study should be executed to reveal the key factors determining the orientation of transmembrane peptides in membrane.In this thesis,we designed different systems with molelular dynamic simulation method to investigate the intercations between transmembrane peptides and membrane systematically,the key factors affecting the interactions were discussed,at the same time we established a method to predict the orientation of the transmembrane peptides,by studying the intercations of the phospholipid bilayer membrane and the peptides.Firstly,we placed the sigle-helix transmembrane peptide on the surface of the membrane to study the spontaneous insertion process with a long time molecular dynamics simulation.After 1.0 ?s MD simulation completes,no higher extent of membrane insertion is observed,we speculated that there is an energy barrier at the interface of membrane – water,which preventing peptide chain spontaneous into the membrane.Moreover,for the purpose of obtaining more accurate statistic data,we launched twelve 100 ns independent MD simulations starting from the same initial configuration with different initial velocity distributions.The statistic informations indicated the C-terminus of the first helix is more easier anchoring on the membrane and then insert into the membrane.Since it is difficult to acquire the complete insertion process with the molecular dynomic simulatoin,so we exerted a external pull force on both ends of the peptide,respectively,thereby the peptide was capable of access to membrane quickly.By comparing the variation of the force in the pulling process,we have further found that the C-terminal of the first helix chain was more easier to overcome the energy barrier and inserted into the membrane.The damage of the peptide and membrane in the pulling peptide chain simulation made the result unsuitable to energy analysis,so the peptide was inserted into the membrane at different depth,and then a spontaneous silulation was carried out to determine and compare the critical depth of the first helix peptide.In this way,we found the critical depth of the C-terminus is less than the N-terminus,this means the former is easier to achieve insertion process than the latter.Finally,in order to explain the mechanism of insertion and the orientation of the transmembrane peptide from thermodynamic point of view,we have measured the varitation of the potential of mean force(PMF)during the insertion process.By analyzing the trend of potential of mean force,it indicate that the C – terminus of the peptide tend to penetrate through the membrane more easily from the energy point of view.At last,according to the above mentioned simulation results,we proposed an model to understand the insertion process at molecular level.