Abstract

We present a framework, which we call Molecule Deep Q-Networks (MolDQN), for molecule optimization by combining domain knowledge of chemistry and state-of-the-art reinforcement learning techniques (double Q-learning and randomized value functions). We directly define modifications on molecules, thereby ensuring 100% chemical validity. Further, we operate without pre-training on any dataset to avoid possible bias from the choice of that set. MolDQN achieves comparable or better performance against several other recently published algorithms for benchmark molecular optimization tasks. However, we also argue that many of these tasks are not representative of real optimization problems in drug discovery. Inspired by problems faced during medicinal chemistry lead optimization, we extend our model with multi-objective reinforcement learning, which maximizes drug-likeness while maintaining similarity to the original molecule. We further show the path through chemical space to achieve optimization for a molecule to understand how the model works.

Details

Title
Optimization of Molecules via Deep Reinforcement Learning
Author
Zhou Zhenpeng 1   VIAFID ORCID Logo  ; Kearnes, Steven 2   VIAFID ORCID Logo  ; Li, Li 2 ; Zare, Richard N 3 ; Riley, Patrick 2   VIAFID ORCID Logo 

 Stanford University, Department of Chemistry, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Work done during an internship at Google Research Applied Science, Mountain View, USA (GRID:grid.168010.e) 
 Google Research Applied Science, Mountain View, USA (GRID:grid.420451.6) 
 Stanford University, Department of Chemistry, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2263285301
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.