Prediction method for ubiquitination degradation of target protein

Abstract

The invention relates to a prediction method for the ubiquitination degradation of a target protein. The prediction method comprises the following steps: A1, predicting the interaction of protein subunits by adopting a convolutional neural network method; A2, constructing a spatial three-dimensional structure of the ubiquitin marking system; A3, predicting a ubiquitination-degraded target protein,downloading a three-dimensional structure file of the target protein, complementing the three-dimensional structure of the target protein by using a homologous modeling method, and predicting the interaction between the target protein and a E3 ubiquitination marking system by using the convolutional neural network method; after that, optimizing an overall spatial three-dimensional structure of interaction between the E3 ubiquitin marking system and the target protein by adopting a molecular dynamics method, judging whether the target protein is possibly marked by the E3 ubiquitin marking system or not according to the stability of the system, and performing ubiquitin-target protein marking by virtue of the ubiquitin-target protein marking system, and degrading the protein by virtue of a ubiquitin-proteasome.

Description

technical field [0001] The invention relates to a prediction method for ubiquitination degradation target protein. Background technique [0002] Strategies using drugs to treat disease include antibodies, siRNA, and small molecules to block the activity of disease-causing proteins. Antibodies have very efficient specificity but still struggle with cell penetration. Inhibition of gene expression by using siRNA is a good choice, but the difficulty of its delivery and off-target effects hinder its application. Small chemical molecules are extensively screened and synthesized to bind to specific proteins with the aim of inhibiting their function. However, resistance occurs when small molecule drugs are used frequently, and in some exceptional cases, inhibitors can even lead to accumulation of proteins. In addition, for certain proteins such as Ras, which have key mutations during tumorigenesis and lack of druggable cavities on the surface, it is impossible to develop small mo...

AI Technical Summary

Problems solved by technology

However, at present, only PROTAC molecules can be designed first, and then experiments are used to prove whether the protein can be degraded by the Cullin system of VHL and CRBN

Moreover, the existing PROTACs design method can only achieve the degradation of the target protein by adding an intermediate Linker based on the existing E3 and target protein inhibitors

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