It is the first time to predict the secondary structures of N/C terminuses of p53 protein by referring the secondary structures of their encoding mRNA secondary structures. This work was based on the find that there is a unit numbers corespondent relationship probably existing between the secondary structures of protein and its encoding mRNA which is advanced by Prof. Liu Ci-quan et al in 1998. The result of prediction shows there are four α helix (14-16, 38-46, 51-56, 68-70aa) in the ne-terminal region, and another tow α helix (368-373, 381-388aa) in c-terminal region of p53 protein, no β sheet was found in this two predicted region. These prediction results conformed with the other four methods of protein secondary structure prediction based on the multiple sequence alignment (accuracy = 73.20%) performed by France Institute of Biology and Chemistry of Protein (IBCP). Furthermore, the predicted protein secondary structures were built up into two models of 3-D conformations in SGI-INDIGO~2 workstation. Referring with the experimental data, these models better expound the relations among those biological function domains of p53 N/C terminus at 3-D level. After more than ten years molecular biological researching and testing, a great quantity of the p53 mutation data was accumulated. Selectively utilize these mutation materials, and the data of x-ray diffraction crystal structure of the core domain of p53 protein, we performed a molecular dynamics research on ten different residue substitute models that occurring at three hot spots of Ar175, Arg 249 and Arg 248. The result shows that the core domain of p53 protein keeps its normal conformation during the whole 12ps dynamics progress. This suggested that the core domain of p53 protein not only has a stability of resistant proteolysis but also keeps a higher stability on its molecular mechanics. On the contrast, at the same conditions, most of those residue substitute forms changed their basic 3-D structures after 12ps dynamics progresses. Theirs DNA binding surfaces lost initial functional conformation; some of them even discomposed the sandwich scaffold structure. Due to the residue substitute, the hydrophobic core of p53 protein became exposed, and the whole core domain has a tendency of being distintegrated. The results of this dynamics research directly and substantially enriched the foundations of different characteristics of biochemistry and immunity that exist between wild-type and mutant p53 proteins from 3-D conformation aspect.
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