Method for identifying key flexible amino acids on protein small molecule binding pockets

Abstract

The invention relates to a method for identifying key flexible amino acids on a protein small molecule binding pockets. The method comprises the following steps: step 1, in a protein PDB structure, classifying the protein structure into different subtype clusters through 95% sequence similarity; step 2, overlapping all protein structures in the subtype cluster with the same structure by using a clear biological ligand, and accurately identifying small molecule binding pockets on the protein; step 3, dividing the corresponding binding sites in the same structure subtype cluster of the known 3Dstructure into site binding subtypes according to the binding positions of small molecules; step 4, researching the protein flexibility property by calculating physicochemical and structural parameterdifference characterization factors; and step 5, identifying key flexible residues by using the highest score of a system for forming the protein binding pockets. A set of uniform and unbiased research process system is designed, and a set of systematic mathematical statistical formula is developed to determine the structural flexibility of binding site amino acids at the same position of different structural models.

Description

technical field [0001] The invention relates to the field of computational biotechnology, in particular to a method for identifying key flexible amino acids on protein small molecule binding pockets. Background technique [0002] Protein is the material basis of life, and the three-dimensional structure of protein is the basic condition for reflecting its own biochemical function and cell function. During the process of performing biological functions, proteins constantly change their conformation and produce physical, chemical and biological reactions with the surrounding environment. This structural flexibility feature is closely related to the physiological properties of the protein's own structural and functional domains, molecular recognition and binding mechanisms, and catalytic activity, and plays an extremely important role in the normal physiological functions and biological performance of proteins. [0003] At present, the virtual drug screening technology based o...

AI Technical Summary

Problems solved by technology

However, there are not many studies that systematically explore the conformational flexibility characteristics of proteins as a whole or local regions, determine the binding sites at the amino acid level, and predict the properties of key flexible residues at the atomic level.

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