Mothra: Multiobjective de novo Molecular Generation Using Monte Carlo Tree Search

In the field of drug discovery, identifying compounds that satisfy multiple criteria, such as target protein affinity, pharmacokinetics, and membrane permeability, is challenging because of the vast chemical space. Until now, multiobjective optimization via generative models has often involved linear combinations of different reward functions. Linear combinations solve multiobjective optimization problems by turning multiobjective optimization into a single-objective task and causing problems with weighting for each objective. Herein, we propose a scalable multiobjective molecular generative model developed using deep learning techniques. This model integrates the capabilities of recurrent neural networks for molecular generation and Pareto multiobjective Monte Carlo tree search to determine the optimal search direction. Through this integration, our model can generate compounds using enhanced evaluation functions that include important aspects like target protein affinity, drug similarity, and toxicity. The proposed model addresses the limitations of previous linear combination methods, and its effectiveness is demonstrated via extensive experimentation. The improvements achieved in the evaluation metrics underscore the potential utility of our approach toward drug discovery applications. In addition, we provide the source code for our model such that researchers can easily access and use our framework in their own investigations. The source code and pretrained model for Mothra, developed in this study, along with the Docker image for the Pareto front explorer and compound picker, designed to streamline the selection and visualization of optimal chemical compounds, are released under the GNU General Public License v3.0 and available at https://github.com/sekijima-lab/Mothra.