Insights Into Folding Simulation Of A Miniature Protein At Room Temperature

Protein folding is a crossover research field covering molecular biology, physics andchemistry etc. By simply primary structure folding into a given three-dimensional space structure,many reasons (such as pressure, temperature, solvent effects etc.) may bring in misfolding ofproteins. As we know, the misfolding may cause a variety of human diseases, including mad cowdisease, senile dementia and Parkinson’s disease, etc. The study of the mechanism about proteinsfolding can make important contributions to the prevention of disease and the drug design.In regard to protein folding, besides various experimental techniques such as X-ray crystaldiffraction, nuclear magnetic resonance spectra（NMR）, 3D image restructuring based onelectron microscope, scanning tunneling microscopy techniques(STM), computer simulation alsoplays an irreplaceable role. Along with the increase of the computing power, the research ofprotein folding with full atomic molecular dynamics simulation has been widely accepted.Nowadays, molecular dynamics (MD) simulation has been widely applied to study the folding ofthe proteins and protein–ligand binding free energy, it can provide rich detailed information at anatomistic level.In order to know the change process of the structure of protein molecules accurately, thecomputer simulation method has more obvious advantages than the traditional theory andexperiment method. Protein system is a huge multiparticle system, the existence of chemicalbonds and many of the interaction make the interrelation between residues complicated. Mostproteins fold into an active protein with special structure from a stretch of peptide chains is notachieved overnight, but after many a middle state. Many researchers want to track down thewhole process of protein re-folding and to capture every intermediate state by the experimentalmethods, this is a very big project. Due to the folding speed is different at different stages, someis more slow, easy to be found and captured. Also some is very fast, this needs to use a variety oftesting technology combined with special equipment to research. If people want to describe thefolding dynamic process quantitatively and produce a protein folding movie, it’s necessary toafter a long hard work. The molecular dynamics simulation in popular computer simulation cansolve this problem, through the analysis of the dynamic evolution path can clearly see the wholefolding dynamic process, it can be made into a small film with protein folding by some software (such as VMD), which saves people’s work time.The computer simulation research of protein folding is a necessary step to study proteinstructure prediction from amino acid sequence to protein space structure, it can make us betterunderstand the formation process of protein structure and the relationship between the proteinstructure and function, and it also has important implications to the function protein design anddrug research. Therefore, the research of this aspect has attracted widespread attentions andbecomes a hot spot in the modern pharmaceutical and bioinformatics research and many adjacentdomains.The small proteins with explicit secondary structures play an important role in the study ofprotein folding, they are the ideal prototypical system for computational simulations of proteinfolding. The study of a protein folding process under room temperature can be used to elaborateprotein folding mechanism clearly. Room temperature is more close to the actual environment. Inthis report, we have carried out 15ns molecular dynamics (MD) simulation of a designed protein(PDB entry: 2I9M) employing the AMBER/FF99SB force field and a generalized-Borncontinuum solvent model at room temperature. We run minimization before molecular dynamics(MD) simulation, initially steepest descent minimization followed by conjugate gradientminimization. Then temperature is rised from 0K to 300K within 120ps. Finally we perform MDsimulation at a constant temperature of 300K. The result shows that this peptide successfullyfolds into its native state in 6.4ns.This thesis is composed by five chapters. In the first chapter, the composition of the protein,the space structure of the protein and some interaction forces are introduced. The protein foldingview, models, and the folding disease are described in the second chapter. Theories and methodsused in the study, including molecular mechanics method and MD simulation method etc, areintroduced in the third chapter. From the fourth chapter to the sixth chapter, the computationalwork and the main computational results are presented. The fourth chapter discusses a smallprotein folding using molecular dynamics simulation method at room temperature. The fifthchapter draws a conclusion for the whole work and views the future development of the studyconcerning protein folding and MD simulation.