Leveraging computational methods to generate small molecules with desired properties has been an active research area in the drug discovery field. Towards real-world applications, however, efficient generation of molecules that satisfy multiple property requirements simultaneously remains a key challenge. In this paper, we tackle this challenge using a search-based approach and propose a simple yet effective framework called MolSearch for multi-objective molecular generation (optimization). We show that given proper design and sufficient information, search-based methods can achieve performance comparable or even better than deep learning methods while being computationally efficient. Such efficiency enables massive exploration of chemical space given constrained computational resources. In particular, MolSearch starts with existing molecules and uses a two-stage search strategy to gradually modify them into new ones, based on transformation rules derived systematically and exhaustively from large compound libraries. We evaluate MolSearch in multiple benchmark generation settings and demonstrate its effectiveness and efficiency.
Keywords: Applied computing → Bioinformatics; Computing methodologies → Machine learning algorithms; Design Moves; Molecular Generation and Optimization; Monte Carlo Tree Search.