Computational Analysis Of Intracellular Protein Stability Based On Sequence-Derived Features

There are closed relationship between protein degradation and many cellular processes such as cellproliferation and differentiation, signal transduction and so on. The Ubiquitin-proteasome pathway isthe major protein degradation pathway in eukaryote. And there are closed relationship between proteindegradation and its inherent sequence and structure information. This paper considers theprotein-protein interaction domains are often exposed to the surface in the there-dimensional structureof peotein, and the protein functions are often closely related with the surface features of itsthree-dimensional structure. So this paper researched the stability of eukaryotic protein from thesequence and structure characteristics of protein surface and low depth amino acids.(1) After processing the high throughput experimental data, I predicted the solvent accessiblesurface of human proteins based on sequences, and retrieved the surface sequences. To these aminoacids exposed on protein surface, I have analyzed their physical and chemical properties, primarystructure, secondary structure, important motifs, Post-translational modification and N-end amino acids.And I chose some best differentiation features to build a short half-lived protein prediction model in thework, and the sensitivity, specificity and accuracy are77.5%,78.2%and78.2%, and comparativelyanalyzed the results of the SProtP model built by our lab and the results of the model built by N-endrule.(2) The protein conformation is not fixed in cells and it can change with the function plays. Theamino acids which located near the protein surface can move to the surface, to this phenomenon,according to the three-dimensional structure of proteins, I calculated the depth of each atom, and gotthe low depth sequences. Analyzing the relationship of protein stability and the characters of low depthprotein and it showed that there are some relationship between some features of low depth protein andprotein stability, such as in the short-lived proteins, there are more uncharged amino acids in the lowdepth protein and in the long-lived proteins, there are more charged amino acids in the low depthproteins, and the stability of hydrogen bonds between them are not the same.(3) I have wrote a tool using CGI programming for calculating the amino acids depth, subscriberscan calculate the depth of amino acids conveniently through it, and then can deeply understand therelation between characters of protein structure and function.