The Research On Template Design And Classification Method Of Bromodomain-like Folding Type

The study of protein folding pattern is a major frontier of life science, the folding classification is the foundation of the research of protein folding. The systematic study on the of protein folding types, which will provide the basis for the functional classification and prediction of protein.The results can be used to the predict of protein spatial structure, reduce the searching range of protein three level structure prediction and accelerate the search speed. Bromodomain protein is the only domain in the human body which can bind to lysine acetylation, this kind of protein is in the opposite direction of the four helix bundle and highly conserved in structure. So it is meaningful to study the Bromodomain-like protein folding type for protein folding in structure. The following two aspects of the folding type are studied:1. The template design of Bromodomain-like folding typeFor the problem that the universal shortage of natural template for folding type classification, we present the design method of the Bromodomain-like folding type template.We chose 52 Bromodomain-like folding type samples whose sequence similarity is less than 40% and the resolution is higher than 0.25 nm in the database of the SCOPe of astral 2.03, based on the results of multiple structure alignment and data analysis, established the design method of the folding type family template, used the system clustering method and constructed the clustering graph of family template, and completed the design of the template of the folding type. The results show that: the design templates have universality, and the templates can be used for protein folding type classification.2. The classification method based on design templates of BRD-like folding typeDefect of single template classification method, we constructed a template database of Bromodomain-like folding type, and established a comprehensive classification method based on multiple templates.Our method is used for classification of Bromodomain-like folding type. We tested the training set of 12117 samples, the sensitivity and specificity were 0.923 and 0.997 respectively, the MCC was 0.72. Then we tested the 2260 samples of the independent test, the sensitivity and specificity were 0.941 and 0.998 respectively, and the MCC was 0.86. The result indicated that: the comprehensive classification method based on multiple templates can be used for the classification of protein folding.We studied one kind of folding type of Bromodomain-like, introduced a complete template design method, and completed the design of the folding type template. The constructed templates were universal, overcame the limitations of the nature templates and eliminated the negative effects of other structures other than folding core. Besides, we proposed a method of multi template based on designtemplate, which overcome the defects based on single template classification method and improved the MCC value, sensitivity and specificity.