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- E-ISSN 2288-8985
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2D-QSAR analysis for hERG ion channel inhibitors
Analytical Science and Technology / Analytical Science and Technology, (P)1225-0163; (E)2288-8985
2011, v.24 no.6, pp.533-543
https://doi.org/10.5806/AST.2011.24.6.533
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(2011). 2D-QSAR analysis for hERG ion channel inhibitors. Analytical Science and Technology, 24(6), 533-543, https://doi.org/10.5806/AST.2011.24.6.533
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Abstract
The hERG (human ether-a-go-go related gene) ion channel is a main factor for cardiac repolarization, and the blockade of this channel could induce arrhythmia and sudden death. Therefore, potential hERG ion channel inhibitors are now a primary concern in the drug discovery process, and lots of efforts are focused on the minimizing the cardiotoxic side effect. In this study, IC_(50) data of 202 organic compounds in HEK (human embryonic kidney)cell from literatures were used to develop predictive 2D-QSAR model. Multiple linear regression (MLR), Support Vector Machine (SVM), and artificial neural network (ANN) were utilized to predict inhibition concentration of hERG ion channel as machine learning methods. Population based-forward selection method with cross-validation procedure was combined with each learning method and used to select best subset descriptors for each learning algorithm. The best model was ANN model based on 14 descriptors (R^2_(CV)=0.617, RMSECV=0.762, MAECV=0.583) and the MLR model could describe the structural characteristics of inhibitors and interaction with hERG receptors. The validation of QSAR models was evaluated through the 5-fold cross-validation and Y-scrambling test.
- keywords
- 2D-QSAR, hERG ion channel inhibitor, machine learning, MLR, SVM, ANN, cross-validation
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