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KMID : 0385520110240060533
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Analytical Science & Technology
2011 Volume.24 No. 6 p.533 ~ p.543
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2D-QSAR analysis for hERG ion channel inhibitors
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Jeon Eul-Hye
Park Ji-Hyeon
Jeong Jin-Hee
Lee Sung-Kwang
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Abstract
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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, IC50 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 (R2 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.
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KEYWORD
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2D-QSAR, hERG ion channel inhibitor, machine learning, MLR, SVM, ANN, cross-validation,
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