Research On The Mechanism Of Action Of Protein Components Of Traditional Chinese Medicine Based On Bioinformatics

Background:The application of traditional Chinese medicine(TCM)has a long cultural background and the support of clinical efficacy,it has the advantages and characteristics of multiple components,multiple targets.The study on the therapeutic material basis and mechanism of TCM is based on modern analytical methods and pharmacology to explain the effective parts and improve the quality control of TCM and its development and application.As one of the main effective components of TCM,protein and its hydrolysate have pharmacological activities,so it is an important development direction to develop the research value of protein components in TCM.On the other hand,natural amino acids as a class of substances that have biological activity as well as maintain the growth of the organism,are used as drug substances,but some physicochemical properties of amino acids hinder their clinical application,so the structural modification of amino acids is a prerequisite for their extensive application.The study of oligopeptides is a feasible way to solve the above problems,because the advantages of fast transfer speed and high tissue penetration,oligopeptide drug is the key direction of drug discovery.It is a new way to solve the deficiency of amino acid drugs and to explain the material basis and mechanism of protein in traditional Chinese medicine.Objective:In order to obtain the optimal oligopeptide compounds for targeting the disease targets,and explain the effective components and effective parts of TCM protein from the point of view of bioinformatics.Besides,explain the mechanism of the TCM protein by the structural similarity between the screening oligopeptides and the hydrolysate of TCM protein.Methods:Virtual screening is the use of computer programs for the screening of compound molecules to reduce the actual number of screening compounds,while improving the efficiency of the discovery of lead compounds.Molecular docking is the process of identifying between the receptors and ligands by energy matching and spatial matching.The conformational search methods are based on high temperature molecular dynamics and simulated annealing algorithm,and scoring and screening of receptor-ligand binding conformations are based on CHARMm forcefield.Screening method of oligopeptide library is select the optimal compounds as the structural basis from amino acids screening,to modify the structures by adding the amino acid residues to achieve oriented oligopeptide library screening,the test was end with the scoring function-ECD value no longer increases.Results:Type 2 diabetes mellitus and metabolic syndrome related disease targets PTP1B and PPARα/γ were used as the experimental targets,the trp,asp,glu-hexapeptides PTPIB inhibitors and trp-tetrapeptides PPARα/γ dual agonists were obtained,and the mechanism of simulated hydrolysis oligopeptide product of soybean protein,buckwheat protein and donkey-hide gelatin protein on PTP1B and PPARα/γ were analyzed based on the molecular docking and structural characteristics.Conclusions:In this study,semi flexible molecular docking was used to incremental screening of oriented oligopeptide library,this screening method can obtain oligopeptide drugs efficiently and quickly,and provide effective lead compounds for clinical drug research.To compare and validate the results of structure similarity between the simulate hydrolyze oligopeptide products and screened oligopeptides,can be used to the study of therapeutic material basis and mechanism of action based on bioinformatics,and provide a new research direction and idea for reaearch methods based on traditional experiments.