Desirable molecule discovery via generative latent space exploration

Abstract

Drug molecule design is a classic research topic. Drug experts traditionally design molecules relying on their experience. Manual drug design is time-consuming and may produce low-efficacy and off-target molecules. With the popularity of deep learning, drug experts are beginning to use generative models to design drug molecules. A well-trained generative model can learn the distribution of training samples and infinitely generate drug-like molecules similar to the training samples. The automatic process improves design efficiency. However, most existing methods focus on proposing and optimizing generative models. How to discover ideal molecules from massive candidates is still an unresolved challenge. We propose a visualization system to discover ideal drug molecules generated by generative models. In this paper, we investigated the requirements and issues of drug design experts when using generative models, i.e., generating molecular structures with specific constraints and finding other molecular structures similar to potential drug molecular structures. We formalized the first problem as an optimization problem and proposed using a genetic algorithm to solve it. For the second problem, we proposed using a neighborhood sampling algorithm based on the continuity of the latent space to find solutions. We integrated the proposed algorithms into a visualization tool, and a case study for discovering potential drug molecules to make KOR agonists and experiments demonstrated the utility of our approach.