Molecular Dynamics Simulation Of Human Glucagon Like Peptide-2

Molecular dynamics simulation is a simulation method that uses computer software and takes the motion of molecules as the simulation object based on the classical Newtonian mechanical equation.Molecular dynamics simulation can not only obtain the molecular trajectory,but also observe the micro details of atomic motion,which can not be obtained by theoretical calculation and experimental methods.It can be said that molecular simulation is a favorable supplement to the traditional methods of studying molecular systems.In recent years,with the rapid development of computer science and information technology,the accuracy of computer has been greatly improved,which makes the application scope of molecular dynamics simulation more and more extensive.At present,molecular dynamics simulation has occupied an important position in biophysics,condensed matter physics and drug design,and has become an indispensable and important research tool.Under the background that molecular dynamics simulation is widely used,we want to further understand the application of molecular dynamics simulation in protein conformational change.As we all know,the sequence of amino acids and the spatial three-dimensional structure of proteins determine the specificity of proteins,and the structural basis of proteins determines the biological function basis of proteins.At present,PDB(protein data bank)protein database has collected a large number of protein crystal structures,which provides convenience for us to study protein conformational changes by molecular dynamics simulation.There is a continuous process when the protein performed its biological function,the traditional experimental methods ca not observe the dynamic process of protein changes,but the molecular dynamics simulation method can observe the interaction between amino acids,conformational changes and protein movement trend at the atomic level.GLP-2 has important biological functions and has a beautiful helical structure.Although the biological function of GLP-2 has been studied a lot,there is little information about the spatial structure of GLP-2.At present,there are few articles on GLP-2 molecular dynamics at home and abroad.The physiological environment of protein is complex and diverse.In order to further understand the influence of external physical or chemical conditions on the spatial structure of GLP-2,this paper uses the method of molecular dynamics simulation to study the molecular dynamics simulation of GLP-2 protein under different physical and chemical conditions.By studying the impact of changes in physiological environment on GLP-2,on the one hand,it can help researchers find a physiological environment suitable for GLP-2 and even enhance its biological activity.On the other hand,when treating diseases involving GLP-2 protein,doctors can take the physiological environment causing GLP-2conformational destruction as a reference basis,so as to avoid affecting GLP-2conformation due to changes in physiological environment,Then the phenomenon of reducing its physiological activity occurs.Therefore,the study of GLP-2 in this paper is of great significance.In this paper,we used GROMACS and charmm36 force field to study the effects of different temperature,electric field intensity and concentration of Na Cl solution on the conformational changes of human glucagon like peptide-2(GLP-2).The root mean square deviation(RMSD),root mean square fluctuation(RMSF),gyration radius(Rg),solvent accessible surface area(SASA),solvent accessible surface area(area),secondary structure and hydrogen bond of the output trajectory file were analyzed.The main research conclusions of this paper include:(1)Molecular dynamics simulation of GLP-2 at different temperatures.The results shown that the ?-helix structure of GLP-2 was destroyed with the increase of temperature.Below 320 K,the conformation of GLP-2 was basically unchanged;Under the high temperature conditions of T = 400 k and T = 500 K,the ?-helix structure was seriously damaged.The higher the temperature was,the more serious the conformation of GLP-2 was destroyed.Temperature was an important reason for protein denaturation.When the temperature reached the temperature of protein denaturation,with the increase of temperature,the hydrogen bond between protein structures was destroyed and the spatial structure was destroyed,resulting in irreversible denaturation of protein.(2)Molecular dynamics simulation of GLP-2 at different strength electric fields.We added electric fields(0V/nm?E?1V/nm)in the z-axis direction of GLP-2,founding that E = 0.5v/nm was an inflection point,In the range of 0V/ nm <E?0.5V/nm,the damage range of helical structure increased with the increase of electric field intensity,Under the condition of E = 0.5v/nm,the electric field had the greatest influence on the spatial structure of GLP-2,In the range of 0.5V/nm < E?1V/nm,the range of spatial structure changes of GLP-2 did not continue to increase with the enhancement of the electric field.Residues at positions 1,3,8,9,20,21,33 of GLP-2 protein are charged.These charged residues were affected by the electric field,and their internal hydrogen bonds were broken,which resulting in changes in protein structure.(3)Molecular dynamics simulation of GLP-2 in different concentrations of Na Cl solution.We established four different systems: n=0,n=5000,n=10000 and n=15000.Through the analysis of the results of the simulated systems,we found that at low Na Cl concentration,ions had nonspecific electrostatic interaction with proteins,which played a role in stabilizing protein structure.At high ion concentration,ions were harm to protein stability.