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Virtual screening method for micromolecular reversible inhibitor of alkaline metalloproteinase from flavobacterium YS-80-122

A basic metal and virtual screening technology, which is applied in special data processing applications, instruments, electrical digital data processing, etc., can solve difficult problems in the research field, and achieve the effect of fast screening methods, high reliability, and good pertinence

Inactive Publication Date: 2014-03-19
YELLOW SEA FISHERIES RES INST CHINESE ACAD OF FISHERIES SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no ready-made specific screening model and structural information database for industrial enzyme reversible inhibitors, which has always been a difficult problem in the research field.

Method used

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  • Virtual screening method for micromolecular reversible inhibitor of alkaline metalloproteinase from flavobacterium YS-80-122
  • Virtual screening method for micromolecular reversible inhibitor of alkaline metalloproteinase from flavobacterium YS-80-122
  • Virtual screening method for micromolecular reversible inhibitor of alkaline metalloproteinase from flavobacterium YS-80-122

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Effect test

Embodiment 1

[0029] Embodiment 1 Purification of Flavobacterium YS-80-122 Alkaline Metalloprotease: Utilize Flavobacterium YS-80-122 to obtain the method of Alkaline Metalloprotease, can refer to literature (Zhang S C, Sun M, Li T, et al.Structure Analysis of a new psychrophilic marine protease[J].PloS one,2011,6(11):e26939.)

[0030] Flavobacterium YS-80-122 alkaline metalloprotease was purified by membrane ultrafiltration and molecular sieve gel chromatography (Superdex200). During the purification process, the enzyme activity was detected using azo-casein as a substrate. The reaction temperature of the enzyme was 30°C, and the reaction contained 400 μL 0.1mol / l Tris-HCl buffer (pH9), 250 μL enzyme solution and 100 μL 1% ( w / v) of the substrate solution, trichloroacetic acid was used to terminate the reaction. The absorbance value of the reacted solution was measured at 345nm, and one unit of enzyme activity was defined as the amount of enzyme needed to increase the absorbance by 0.01 u...

Embodiment 2

[0032] A screening method for small molecule reversible inhibitors derived from Flavobacterium YS-80-122 alkaline metalloprotease, comprising the following steps

[0033] (1) Determine the class of small molecule reversible inhibitors based on the known structural data of the alkaline metalloprotease derived from Flavobacterium YS-80-122; test the class of small molecule reversible inhibitors against Flavobacterium YS-80-122 Inhibition constants of alkaline metalloproteinase activity, according to the test data (Table 1), determine the constituent compounds of the training set;

[0034] Boronic acid and other boron-derived compounds have always been one of the important sources of protease inhibitors because of their good inhibitory activity. This embodiment tests the inhibitory effect of 18 kinds of boric acid derivatives on Flavobacterium YS-80-122 alkaline metalloprotease, and the results are shown in Table 1:

[0035] Table 1. Inhibition constants of boric acid derivative...

Embodiment 3

[0060] Example 3 Inhibition constants and inhibition types of compounds ZINC01006243, ZINC03025346 and ZINC02961282

[0061] Three of the compound molecules were synthesized: ZINC02961282, ZINC03025346 and ZINC01006243, and their inhibition constants were tested as: 0.84±0.13, 1.02±0.044 and 1.28±0.055mmol, and after adding different concentrations of inhibitors, the maximum reaction speed V m Keep consistent, Michaelis constant K m Positively correlated with the concentration of the inhibitor, all belong to reversible inhibition. The test results of its inhibition constant are as follows figure 2 , and the model diagram of the interaction with metalloproteinases is shown in the appendix image 3 .

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Abstract

The invention relates to a virtual screening method for a micromolecular reversible inhibitor of an alkaline metalloproteinase from flavobacterium YS-80-122 and belongs to the field of marine biotechnologies. The virtual screening method comprises the following steps: determining the type of the micromolecular reversible inhibitor according to the known structural data of the alkaline metalloproteinase from the flavobacterium YS-80-122; measuring the inhibition constant of the micromolecular reversible inhibitor of the type to the alkaline metalloproteinase from the flavobacterium YS-80-122, and determining compounds composing a training set; conducting molecular docking on the compounds of the training set and the alkaline metalloproteinase from the flavobacterium YS-80-122; acquiring the theoretical binding free energy and the theoretical reversible inhibition constant of the compounds of the training set and the alkaline metalloproteinase from the flavobacterium YS-80-122; in combination with the measured data, making a screening rule and establishing a screen model; conducting virtual screening. The virtual screening method is high in screening speed, can quickly reduce the quantity of candidate molecules, and reduce waste of time and test materials.

Description

technical field [0001] The invention belongs to the technical field of marine biology, and in particular relates to a virtual screening method for small-molecule reversible inhibitors, in particular to a virtual screening method for small-molecule reversible inhibitors with Flavobacterium YS-80-122 alkaline metalloprotease as a binding target. Background technique [0002] Enzymes are characterized by less dosage, high catalytic efficiency and strong specificity. After more than half a century of rapid development, the enzyme preparation industry has now formed a dynamic high-tech industry, which is widely used in food, textile, washing, papermaking, feed and bio-energy industries. At present, liquid enzyme preparation technology saves about 30% to 50% of water and more than 50% of energy in the manufacturing process of similar products, which is more in line with the development needs of low-carbon economy; there is no doubt that high-activity, high-purity, liquid enzymes w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G06F19/10
Inventor 纪晓峰郑媛孙谧郝建华盛军
Owner YELLOW SEA FISHERIES RES INST CHINESE ACAD OF FISHERIES SCI
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