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Consistency model building method based on 3-dimensional quantitative structure-activity relationship model

A technology of structure-activity relationship and construction method, applied in the field of bioinformatics, can solve problems such as not being able to contain all the information of compounds, and the prediction accuracy of a single model is not high, and achieve the effect of improving the prediction ability

Inactive Publication Date: 2015-08-12
BEIJING UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Aiming at the problem that the single model of CoMFA, CoMSIA and Topomer CoMFA cannot contain all the information of the compound and the prediction accuracy of the single model is not high, the consistency model proposed by the present invention can improve the quality of the model, improve the prediction ability and stability of the model

Method used

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  • Consistency model building method based on 3-dimensional quantitative structure-activity relationship model
  • Consistency model building method based on 3-dimensional quantitative structure-activity relationship model
  • Consistency model building method based on 3-dimensional quantitative structure-activity relationship model

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Experimental program
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Embodiment 1

[0030] The present invention relates to the use of HIV-1 integrase inhibitor compound molecules derived from (POLANSKI J, ZOUHIRI F, JEANSON L, DESMAELE D, D'ANGELO J, MOUSCADET J F, GIELECIAK R, GASTEIGER J, LE BRET M.Use of the Kohonen neural network for rapid screening of ex vivo anti-HIV activity of styrylquinolines[J].Journal of Medicinal Chemistry,2002,45(21):4647-4654; NORMAND-BAYLE M,BENARD C,ZOUHIRI F,MOUSCADET J F,LEH H ,THOMAS C M,MBEMBA G,DESMAELE D,D'ANGELO J.New HIV-1replication inhibitors of the styryquinoline class bearing aroyl / acyl groups at the C-7position:Synthesis and biological activity[J].Bioorganic&Medicinal Chemistry Letters,2005,15 (18):4019-4022; LEONARD J T,ROY K.Exploring molecular shape analysis of styrylquinoline derivatives as HIV-1 integrase inhibitors[J].Eur J Med Chem,2008,43(1):81-92;MOUSCADET J F,DESMAELE D.Chemistry and Structure-Activity Relationship of the Styrylquinoline-Type HIV Integrase Inhibitors[J].Molecules,2010,15(5):3048-3078; O...

Embodiment 2

[0080] According to the data of HIV-1 entry inhibitor 3D-QSAR model in the literature (C.Teixeira, N.Serradji, F.Maurel, F.Barbault, Docking and 3D-QSAR studies of BMS-806analogs as HIV-1gp120entry inhibitors, European Journal of Medicinal Chemistry 44(2009) 3524–3532.), Constructing Consistency Models.

[0081] Using biostatistical methods, the 3D-QSAR model training set compound molecular pIC 50 The predicted value of is used as the independent variable, and the experimental measurement value is used as the dependent variable. The formula for obtaining the consistency model is shown in formula 12.

[0082] pIC 50 =0.736×P CoMFA +0.582×P CoMSIA -0.111 (12)

[0083] Using statistical software, substitute the pIC50 value of CoMFA and CoMSIA prediction set compound molecules into formula (12), and calculate the predicted value of the consistency model prediction set molecules.

[0084] The predicted value of the consistency model test set is used as the independent variable...

Embodiment 3

[0086]In this example, the data of 3D-QSAR models of 90 HIV inhibitors in recent years were collected, and the predicted values ​​and experimental values ​​of the 3D-QSAR models in the training set and prediction set in the literature were used to construct the consistency model. Since the value of Topomer CoMFA has a strong correlation with the values ​​of CoMFA and CoMSIA models, after the consistency model is constructed, only the consistency model is compared with the values ​​of CoMFA and CoMSIA models, and the comparison is based on the cross-validation correlation of the original model. Coefficient q 2 The size is divided into 0.52 ≤0.6; 0.62 ≤0.7; 0.72 ≤0.8; 2 >0.8 four categories. After eliminating suspicious values, analyze them respectively according to the above four categories and the five methods without classification.

[0087] The results of testing the consistency model and the CoMFA model with the paired t test method are shown in Table 4. The cross-valida...

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Abstract

The invention relates to a building method of a 3-dimensional quantitative structure-activity relationship (3D-QSAR) model, in particular to building of the 3D-QSAR model based on HIV-1 inhibitor molecules and consistency model building, and belongs to the technical field of biological information. The HIV-1 inhibitor molecules are selected to perform 3D-QSAR and consistency model research so as to mine the relationship between the structure of an inhibitor and the anti-HIV activity of the inhibitor. According to the method, the bioactivities of compounds with similar structures are predicted through building of a mathematical model based on the chemical characteristics (such as hydrophilcity, hydrophobicity, electrostatic property, polarity and three-dimensional structure) of the inhibitor. A consistency model is built with a statistics method on the basis of three 3D-QSAR models, and the aim is to further enhance the prediction capability of the model. The obtained model can better predict the anti-HIV activities of compounds, and the prediction accuracy of the anti-HIV activity of a brand new compound is increased. Compared with other methods, the method has the advantages that the medicament discovery efficiency is increased, and the medicament discovery cost is reduced.

Description

technical field [0001] The invention relates to a method for constructing a three-dimensional quantitative structure-activity relationship model, in particular to the establishment of a three-dimensional quantitative structure-activity relationship model based on HIV-1 inhibitor molecules and the construction of a consistency model, belonging to the technical field of biological information. Background technique [0002] Acquired Immunodeficiency Syndrome (Acquired Immunodeficiency Syndrome, AIDS, also known as AIDS) is widely spread around the world, threatening people's life and health, so it is urgent to strengthen the human immunodeficiency virus (Human Immunodeficiency Virus, hereinafter referred to as HIV) Basic biological research, vaccine development and anti-AIDS inhibitor research. [0003] Human immunodeficiency virus type 1 (hereinafter referred to as HIV-1) is a highly mutated retrovirus. HIV infection of host cells is a complex process, including multiple steps...

Claims

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Application Information

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IPC IPC(8): G06F19/12
Inventor 谭建军张一平门婧睿
Owner BEIJING UNIV OF TECH
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