Deep Convolutional Generative Adversarial Network (dcGAN) Models for Screening and Design of Small Molecules...

A deep convolutional generative adversarial network (dcGAN) model was developed in this study to screen and design target-specific novel compounds for cannabinoid receptors. In the adversarial process of training, two models, the discriminator D and the generator G, are iteratively trained. D is trained to discover the hidden patterns among the input data to have the accurate discrimination of the authentic compounds and the "fake" compounds generated by G; G is trained to generate "fake" compounds to fool the well-trained D by optimizing the weights for matrix multiplication of data sampling. In order to determine the appropriate architecture and the input data structure for the involved convolutional neural networks (CNNs), the combinations of various network architectures and molecular fingerprints were explored. Well-developed CNN models including LeNet-5, AlexNet, ZFNet, and VGGNet were investigated. Four types of fingerprints, including MACCS, ECFP6, AtomPair, and AtomPair Count, were calculated to describe the small molecules with diverse structural characteristics. The limitation of generating fingerprints as output remains that the concrete molecular structures cannot be converted directly, while the generative models with convolutional networks provide promising opportunities to the screening of molecules and rational modifications afterward. This study demonstrated how computer-aided drug discovery could benefit from the recent advances in deep learning.