Analysis Of Intrinsically Disordered/Ordered Regions Of Proteins Coded By Disease Related Genes

Intrinsically disordered proteins(IDPs)are a kind of special protein that lack stable three-dimensional structures under physiological conditions.IDPs perform important functions in life activities and are closely related to human diseases.Studies have shown that many of the diseases-related proteins are intrinsically disordered proteins.But due to the flexible structures,there is no efficient experimental and computational tools for IDPs studies.Therefore most disease related studies only focused on a small number of proteins.In order to reveal the relationships between diseases and intrinsically disordered proteins,comprehensive analysis of IDPs in disease related genes was performed based on experimentally confirmed renal cancer and cervical cancer related genes in this paper.The disordered/ordered regions and the potential binding sites are annotated both at protein and CDS sequences level based on bioinformatics methods.On the basis of above analysis,we constructed the first database for disease-related genes and intrinsically disordered proteins,which provide efficient data resources for the intrinsically disordered protein related research.Main work of the thesis is summarized as follows:1.Distribution analysis of intrinsically disordered proteins in disease related proteinsThe disease related protein sequences and their corresponding CDs sequences were obtained based on the experimentally verified gene databases of renal cancer and cervical cancer respectively,from with the CDS and encoded protein data sets of renal cancer(211)and cervical cancer(781)were constructed finally.Based on the datasets,the intrinsically disordered regions are derived from Disprot database,MobiDB database and SPOT-Disorder program respectively.The results showed that 119 items(56.40%)of the renal cancer proteins and 558 items(71.45%)of the cervical cancer proteins were annotated as IDPs.This indicated that the intrinsically disordered proteins are abundant in both cancer gene databases,which was consistent with recent studies of intrinsically disordered proteins.2.Binding sites analysis of disease related proteinsTo study potential links between intrinsically disordered proteins and disease,the binding sites of different molecules in disordered/ordered regions are annotated based several bioinformatics programs.The results indicated that binding sites were predicted in most sequences at protein level.Further analysis showed that the binding sites preferred the ordered regions in the most sequences.For comparison,the DNA--transcription factor binding sites at nuclei acid level were also predicted in 491 DNA sequences,further analysis of the sequences that both ordered and disordered regions contained binding sites revealed that more DNA-transcription factor binding sites preferred disorder regions.3.Construction of web sources of disease-related genes and intrinsic disordered proteinsBased on the above studies,we constructed the first database of disease-related genes and intrinsically disordered proteins,which can be accessed by http://biophy.dzu.edu.cn/D-Disprot/index.php.In current version,677 disease-related genes and their encoding proteins are adopted,of which 119 are renal cancer genes and 558 are cervical cancer genes.The database provides information of ordered/disordered regions of each gene at both nucleic acid and protein levels,and provides the corresponding prediction information of the interaction sites.This database provides helpful data source for future intrinsically disordered proteins and disease researches.