The Computer Simulation Study Of Villin Headpiece Subdomain

Protein folding refers to the process of protein to obtain the functional structure and conformation. That is how the protein folds into a three-dimensional structure with biological functions from a simple peptide chain with non-biological functions. At present, the protein folding can be studied experimentally through a variety of experimental methods, mainly X-ray crystallography, NMR spectroscopy, electron microscopy 3D reconstruction, scanning tunneling microscopy and UV fluorescence technology. The computer simulation based on the theory plays an irreplaceable role.We use the molecular dynamics simulation software GROMACS to study the Villin headpiece subdomain. We simulate the wild-type and mutant protein unfolding in the high temperature, respectively. And then, we start to simulate double mutant protein HP-35_NleNle folding at room temperature. The main contents of thesis include followings:We use the properties of Isoleucine and Lysine to build the Norleucine’s force field parameters before simulation, because the non-standard residues can’t be identified.We adopt the united-atom force field GROMOS96 43al to simulate the protein unfolding of HP-36, HP-35_Nle and HP-35_NleNle in high temperature. The three a-Helix structures disappear quickly and appear β-Sheet structure later. It has little difference in Rg, RMSD and SASA. Due to the GROMOS96 43al force field do not explicitly have all hydrogen atoms and only calculates the heavy atoms combined with hydrogen atoms. It is not precise enough to the small protein like HP-35/36.In the protein unfolding of HP-36 and HP-35_NleNle with all-atom force field AMBER03 in high temperature. It has big differences in unfolding process of HP-36 and HP-35_NleNle. The Rg. RMSD and SASA in HP-36 unfolding simulation is larger than HP-35_NleNle. The results suggest that Norleucine has a stabilizing effect for protein structure.We obtain the three groups of different initial conformations from unfolding simulation. In the folding of HP-35 NleNle with AMBER03 force field at room temperature, we find the process of protein folding is associated with initial conformations. In the process of protein folding, the hydrophobic residues Phe47, Phe51, Phe58, Leu61 and Leu69 quickly close to form the hydrophobic core. The C-terminal helix forms firsts, followed by the N-terminal helix. The middle helix forms last.