ReBADD-SE: Multi-objective molecular optimisation using SELFIES fragment and off-policy self-critical sequence training. (May 2023)

• Record Type: Journal Article
• Authors: Choi, Jonghwan; Seo, Sangmin; Choi, Seungyeon; Piao, Shengmin; Park, Chihyun; Ryu, Sung Jin; Kim, Byung Ju; Park, Sanghyun
• Is Part Of: Computers in biology and medicine. Volume 157(2023)
• Publication Date: 2023-05
• Subjects: Drug discovery -- De novo drug design -- Multi-objective optimisation -- SELFIES -- Reinforcement learning; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2023.106721
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: The discovery of drugs to selectively remove disease-related cells is challenging in computer-aided drug design. Many studies have proposed multi-objective molecular generation methods and demonstrated their superiority using the public benchmark dataset for kinase inhibitor generation tasks. However, the dataset does not contain many molecules that violate Lipinski's rule of five. Thus, it remains unclear whether existing methods are effective in generating molecules violating the rule, such as navitoclax. To address this, we analysed the limitations of existing methods and propose a multi-objective molecular generation method with a novel parsing algorithm for molecular string representation and a modified reinforcement learning method for the efficient training of multi-objective molecular optimisation. The proposed model had success rates of 84% in GSK3b+JNK3 inhibitor generation and 99% in Bcl-2 family inhibitor generation tasks. Graphical abstract: Highlights: We addressed the difficulty in generating complicated molecules with multi-objectives. We propose the SELFIES fragment parsing algorithm and off-policy SCST algorithm. The model is superior in generating GSK3b+JNK3 and Bcl-2 family inhibitors.