Metalloenzyme active site comparison method based on pharmacophore and alpha-carbon characteristics

Abstract

The invention discloses a metalloenzyme active site comparison method based on pharmacophore and alpha-carbon characteristics. A large number of metalloenzyme crystal structures are collected to construct a metalloenzyme information library, active sites of each metalloenzyme are identified based on a metal ion and solvent accessibility principle, and a pharmacophore characteristic model and an alpha-carbon characteristic model are constructed according to surface atoms and surface amino acids of the active sites; and by performing similarity comparison and crystal structure superposition on the target metalloenzyme and the active site feature model in the metalloenzyme information base, and comprehensively considering similarity scoring and superposed structure features, and other metalloenzymes similar to the active site of the target metalloenzyme are outputted. According to the method, pharmacophore characteristics and structural characteristics of active sites are comprehensively considered, and information of the active sites of the metalloenzyme is accurately and comprehensively represented; and according to the method, when an active site similarity result is obtained, a metalloenzyme crystal structure is superposed, metalloenzyme similar to target metalloenzyme is obtained, visual analysis is more sufficient and detailed, and more clues are provided for drug discovery of the target metalloenzyme.

Description

technical field [0001] The invention relates to the field of computer-aided drug molecular design, in particular to a new method for similarity comparison based on identification and feature extraction of metalloenzyme active sites. Specifically, it is a method for comparing active sites of metalloenzymes based on pharmacophore and alpha-carbon features. Background technique [0002] Drug design and discovery targeting metalloenzymes often benefit from the knowledge of their structural information and catalytic mechanism. Since metalloenzymes have their unique and relatively complex catalytic active sites, that is, active sites containing metal ions, analyzing and comparing the active sites of metalloenzymes is of great significance for the development of new and specific metalloenzyme inhibitors. Comparing the active sites of metalloenzymes can also provide reference and help for protein function prediction, drug repurposing and inhibitor selectivity research. Many method...

AI Technical Summary

Problems solved by technology

Although current methods have their own advantages in terms of feature representation and computational accuracy / efficiency, they rarely take into account the metal ion features contained in the active site of metalloenzymes, which makes these methods difficult to achieve when applied to metalloenzymes. expected effect

Images