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Screening Mutational Sites That Enhance Protein Thermostability by High Temperature Molecular Dynamics Method

Author: SongMiaoMiao
Tutor: XiaoZuo
School: Huazhong University of Science and Technology
Course: Theoretical Physics
Keywords: Protein Mutation of residues Thermal stability Dynamics simulation
CLC: Q51-33
Type: Master's thesis
Year: 2011
Downloads: 16
Quote: 0
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Abstract


Protein is an important object of study in the organism function execution, life sciences. All life activities without the involvement of the protein, each protein has to play its function optimum temperature range above or below this temperature range, the activity of the protein will be affected, even inactivation. Present in the food, chemical, molecular design, and biomedical fields, often at higher temperatures will still be able to maintain its original function of the protein, therefore, to improve the thermal stability of the protein, to understand the mechanism of the proteins perform their functions, find protein thermal stability of key factors, the impact has been more than just a scientific issue, in people's daily life and work played an increasingly important role. Attracted a growing number of scientists to spend a lot of time and effort into the study of protein thermal stability. The mutation of the residues is one of the effective ways to improve the thermal stability of the protein. Predicted mutation sites by protein engineering methods, such as reasonable design, a combination of design and data reasoning method, achieved fruitful results. However, how to select the mutation site is still not fully resolved. The efficiency and the effectiveness of the filters also need to further improve. In this paper, using the method of high-temperature dynamics, considering the interaction energy between residues, protein structure and structural information variation with temperature screening to improve the thermal stability of proteins mutations sites. The from ProTherm database selected based on specific criteria, four proteins as research subjects, respectively: 1csp, 1qqv, 1rop 1pga. To 1csp Tm, Tm 50k Tm 100k 150k temperature make Tm dynamics simulation, statistical analysis of the simulation results, elected to do dynamics simulations optimum temperature. Then do the other three proteins at this temperature dynamics simulation, the size of the contribution of thermal stability of protein affect protein thermal stability factors, and these factors, the first to conduct a preliminary screening of protein residues that meet the requirements of the residual group, further analysis of residues of the distance between the variation over time, and then remove the conserved residues, and then get the final results. Less the required data, our method is easy to implement, and the high efficiency, good value. The results of this study show that the electrostatic interaction and hydrophobic effect may be the most important factors to affect the stability of the protein heat.

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CLC: > Biological Sciences > Biochemistry > Protein
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