Study On Modeling The Topology Of Protein Structure And Its Application

3D-structure of protein rules its biological function, and topology is the high level description of the protein structure. Predicting the topology of the protein core not only helps the determination of the3D-structure of protein, but also helps the design and recast of drugs. For the prediction of protein structure, these dissertation studies on modeling the topology of protein structure. One of the studies is to model the topology based on fold mode of protein structure and its application, the other is to model the topology for a specific type of protein structure and its application.Fold mode is a description of topology category of protein structure. Taking the predicted fold of SCOP structure library from a predictor, we construct a high quality fragment library from bases of all structures whose folds are same with the target protein. Such fragment libraries are applied to the prediction of some hard problems in the protein structure prediction. The result shows that the fragment library constructed by our method helps highly improve the accuracy of the protein structure prediction.The G-protein-coupled receptor (GPCR) has very specific topology. The unique7α transmembrane helices determine its main topology. Taking the output of a predictor for the2D-structure of transmembrane helices, we extract3D distance constraints between the transmembrane helices. We also develop another two constrains. One is the orientation between the membrane and helices, and the other is the tilt angle of the helices. A transmembrane helices packing program is then developed in which the three topology constraints are employed. The program is applied in the latest testing and the result shows that it improves the accuracy of prediction structure for transmembrane helices.Our computational method uses the topology of protein fold mode to provide a high quality searching space for assembling protein fragments. Modeling topology of GPCR and the relevant packing method provide a useful tool for the successive applications like GPCR docking.