The power of deep learning to ligand-based novel drug discovery

Deep discriminative and generative neural-network models are becoming an integral part of the modern approach to ligand-based novel drug discovery. The variety of different architectures of neural networks, the methods of their training, and the procedures of generating new molecules require expert knowledge to choose the most suitable approach.

Three different approaches to deep learning use in ligand-based drug discovery are considered: virtual screening, neural generative models, and mutation-based structure generation. Several architectures of neural networks for building either discriminative or generative models are considered in this paper, including deep multilayer neural networks, different kinds of convolutional neural networks, recurrent neural networks, and several types of autoencoders. Several kinds of learning frameworks are also considered, including adversarial learning and reinforcement learning. Different types of representations for generating molecules, including SMILES, graphs, and several alternative string representations are also considered.

Two kinds of problem should be solved in order to make the models built using deep neural networks, especially generative models, a valuable option in ligand-based drug discovery: the issue of interpretability and explainability of deep-learning models and the issue of synthetic accessibility of novel compounds designed by deep-learning algorithms.