Hybrid-genetic algorithm based descriptor optimization and QSAR models for predicting the biological activity of...

The prediction of biological activity of a chemical compound from its structural features plays an important role in drug design. In this paper, we discuss the quantitative structure activity relationship (QSAR) prediction models developed on a dataset of 170 HIV protease enzyme inhibitors. Various chemical descriptors that encode hydrophobic, topological, geometrical and electronic properties are calculated to represent the structures of the molecules in the dataset. We use the hybrid-GA (genetic algorithm) optimization technique for descriptor space reduction. The linear multiple regression analysis (MLR), correlation-based feature selection (CFS), non-linear decision tree (DT), and artificial neural network (ANN) approaches are used as fitness functions. The selected descriptors represent the overall descriptor space and account well for the binding nature of the considered dataset. These selected features are also human interpretable and can be used to explain the interactions between a drug molecule and its receptor protein (HIV protease). The selected descriptors are then used for developing the QSAR prediction models by using the MLR, DT and ANN approaches. These models are discussed, analyzed and compared to validate and test their performance for this dataset. All three approaches yield the QSAR models with good prediction performance. The models developed by DT and ANN are comparable and have better prediction than the MLR model. For ANN model, weight analysis is carried out to analyze the role of various descriptors in activity prediction. All the prediction models point towards the involvement of hydrophobic interactions. These models can be useful for predicting the biological activity of new untested HIV protease inhibitors and virtual screening for identifying new lead compounds.