The Terminal Secondary Structure Predictions of P53 Protein and Hotspots Mutation Dynamics of the Core Domain

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 is based on the fact that there is a unit numbers corespondent relationship probably existing between the secondary structures of protein and its encoding mRNA.The result of prediction shows that there are four α helix(14-16,38-46,51-56,68-70aa)in the n-terminal region,and another tow α helix(368-373,381-388aa)in c-terminal region of P53 protein,no β sheet has been found in this two predicted regions.These prediction results confirmed 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-INDIGO² 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 for molecular biological researching and testing,a great quantity of the P53 mutation data have been accumulated.Selectively utilizing these mutation material and the data of x-ray diffraction crystal structure of the core domain of P53 protein,we have performed a molecular dynamics research on ten different residual substitute models that occurring at three hot spots of Arg 175,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 residual substitute forms changed their basic 3-D structures after 12ps dynamics progresses.Their DNA binding surfaces lost initial functional conformation;some of them even discomposed the sandwich scaffold structure.Due to the residual substitute,the hydrophobic core of P53 protein became exposed,and the whole core domain had a tendency of being disintegrated.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.