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Method for detecting binding specificity between ligand and target and drug screening method

A technology that combines specificity and specificity, which can be used in biological testing, material inspection products, etc., and can solve problems such as side effects and adverse effects.

Inactive Publication Date: 2012-11-28
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Inhibition of Cox2 enzyme activity can effectively reduce inflammation and pain, but non-specific effects on this enzyme can easily lead to serious side effects, and more than tens of thousands of people die or are hospitalized every year
Some drugs on the market have also been withdrawn due to their adverse effects

Method used

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  • Method for detecting binding specificity between ligand and target and drug screening method
  • Method for detecting binding specificity between ligand and target and drug screening method
  • Method for detecting binding specificity between ligand and target and drug screening method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Use COXs as a research system or target to clarify the relevant significance and application of ISR

[0049] We selected 1000 structurally diverse small molecules from the NCI database, and their molecular weights were as close as possible to SC558 (the ligand small molecule in the crystal structure of Cox-2). The structure of SC558 is very similar to Vioxx, Celebrex and Bextra, among which SC558 and Celebrex only differ by one group, that is, the original Br atom is replaced by a methyl group. We use the molecular docking method to study the binding mode of each selected ligand small molecule and Cox-2 molecule, and use Autodock to carry out the corresponding molecular docking calculation. The Cox-2 molecule is rigid and the ligand small molecule adopts a fully flexible strategy. The conformational search of ligand small molecules was done using Lamarck genetic algorithm. Sufficient sampling can ensure the convergence of the final result. The binding free e...

Embodiment 2

[0060] Example 2 Affinity and specificity research on the interaction between levamlodipine and human serum albumin

[0061] The affinity and specificity between drugs and human serum albumin (HSA) are important factors affecting the bioavailability of drugs. Drug-HSA interaction studies have provided a large amount of structural information, but this information is mainly based on molecular size and polarity rather than affinity and specificity. Currently, no studies have shown why site I functions as a fundamental affinity site for the vast majority of small molecules. In order to deeply understand the carrier function of HSA, we used computer simulation to study the interaction between levamlodipine and HAS7 affinity sites. At the same time, the intrinsic specificity ratio (ISR) was used to distinguish the specificity between levamlodipine and HSA7 different sites. By comparing the binding energies and energy spectra of the 7 affinity sites of HSA, levamlodipine has a hig...

Embodiment 3

[0065] Example 3 Using a two-dimensional screening method of affinity and specificity to study inhibitor candidates based on the intermediate conformation of Ras protein

[0066] In this example, based on the intermediate conformation of Ras protein hydrolyzate as the target, the two-dimensional standards of affinity and specificity are used to score, and the method of simulation screening is used to screen out the compounds with high affinity and high ISR value from the NCI small molecule compound library. 26 potential candidate compound small molecules, and in vitro activity research on the obtained small molecules. The implementation of this example proves that the intrinsic specificity value (ISR) as a new specificity standard is suitable for the discovery of lead compounds. This example completes the first virtual screening of drugs based on the intermediate conformation of Ras protein and based on the two-dimensional criteria of affinity and specificity. The discovery o...

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Abstract

The present invention relates to the field of drug screening, and specifically relates to a method for detecting binding specificity between a ligand and a target and a drug screening method. The detection method includes: molecular docking through the ligand and the target, obtaining an energy spectrum of the ligand, introducing the ratio of intrinsic specificity, and thus determining the binding specificity between the ligand and the target. The detection method compared with conventional methods has the advantages of good specificity, high accuracy, fast speed and low cost. The invention provides a new detection method for structure-based virtual drug screening. Based on the detection method, a method of two-dimensional virtual drug screening directed at affinity and specificity is developed. At the same time, the detection method provides a new description characteristic for the side effect research of small molecule compounds, and provides guidance for chemical modification and transform of drug lead compounds. Relative to conventional mere affinity-concerning virtual drug screening, the specificity dimension is added to the method, so the chances of discovery of drug lead compounds are greatly improved.

Description

technical field [0001] The invention relates to the field of drug screening, in particular to a method for detecting the binding specificity of a ligand and a target and a drug screening method. Background technique [0002] The drug discovery process is researched and explored through multidisciplinary interdisciplinary, and its main steps can be summarized as an iterative process from gene to protein and protein to lead compound, and then to lead compound evaluation, optimization and modification. With the continuous development of computer itself and its technology, computer-aided drug design has already become one of the indispensable means in the field of drug discovery, including molecular simulation, combinatorial chemistry, structure-activity relationship, chemoinformatics and data mining and other fields. Using computers to apply various possible methods and theories to search and optimize lead substances, and to chemically modify the resulting lead substances to fu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/50
Inventor 郑喜亮汪劲刘作家李丹汪尔康
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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