Molecular modeling studies of human immunodeficiency virus type 1 protease inhibitors using three-dimensional quantitative structure-activity relationship, virtual screening, and docking simulations

2016 ◽  
Vol 30 (9) ◽  
pp. 523-536 ◽  
Author(s):  
Jianbo Tong ◽  
Pei Zhan ◽  
Min Bai ◽  
Tuanli Yao
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Modeling ◽  
Three Dimensional ◽  
Quantitative Structure Activity Relationship ◽  
Quantitative Structure ◽  
Docking Simulations ◽  
Structure Activity ◽  
Immunodeficiency Virus ◽  
Molecular Modeling Studies

scholarly journals Targeting HIV/HCV Coinfection Using a Machine Learning-Based Multiple Quantitative Structure-Activity Relationships (Multiple QSAR) Method

2019 ◽  
Vol 20 (14) ◽  
pp. 3572 ◽  
Author(s):  
Yu Wei ◽  
Wei Li ◽  
Tengfei Du ◽  
Zhangyong Hong ◽  
Jianping Lin
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mean Value ◽  
Classification Models ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Immunodeficiency Virus ◽  
Quantitative Structure Activity Relationships ◽  
Hcv Coinfection ◽  
Hiv 1

Human immunodeficiency virus type-1 and hepatitis C virus (HIV/HCV) coinfection occurs when a patient is simultaneously infected with both human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV), which is common today in certain populations. However, the treatment of coinfection is a challenge because of the special considerations needed to ensure hepatic safety and avoid drug–drug interactions. Multitarget inhibitors with less toxicity may provide a promising therapeutic strategy for HIV/HCV coinfection. However, the identification of one molecule that acts on multiple targets simultaneously by experimental evaluation is costly and time-consuming. In silico target prediction tools provide more opportunities for the development of multitarget inhibitors. In this study, by combining Naïve Bayes (NB) and support vector machine (SVM) algorithms with two types of molecular fingerprints, MACCS and extended connectivity fingerprints 6 (ECFP6), 60 classification models were constructed to predict compounds that were active against 11 HIV-1 targets and four HCV targets based on a multiple quantitative structure–activity relationships (multiple QSAR) method. Five-fold cross-validation and test set validation were performed to measure the performance of the 60 classification models. Our results show that the 60 multiple QSAR models appeared to have high classification accuracy in terms of the area under the ROC curve (AUC) values, which ranged from 0.83 to 1 with a mean value of 0.97 for the HIV-1 models and from 0.84 to 1 with a mean value of 0.96 for the HCV models. Furthermore, the 60 models were used to comprehensively predict the potential targets of an additional 46 compounds, including 27 approved HIV-1 drugs, 10 approved HCV drugs and nine selected compounds known to be active against one or more targets of HIV-1 or HCV. Finally, 20 hits, including seven approved HIV-1 drugs, four approved HCV drugs, and nine other compounds, were predicted to be HIV/HCV coinfection multitarget inhibitors. The reported bioactivity data confirmed that seven out of nine compounds actually interacted with HIV-1 and HCV targets simultaneously with diverse binding affinities. The remaining predicted hits and chemical-protein interaction pairs with the potential ability to suppress HIV/HCV coinfection are worthy of further experimental investigation. This investigation shows that the multiple QSAR method is useful in predicting chemical-protein interactions for the discovery of multitarget inhibitors and provides a unique strategy for the treatment of HIV/HCV coinfection.

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