MoleGuLAR: Molecule Generation Using Reinforcement Learning with Alternating Rewards.

ABSTRACT

The design of new inhibitors for novel targets is a very important problem especially in the current scenario with the world being plagued by COVID-19. Conventional approaches such as high-throughput virtual screening require extensive combing through existing data sets in the hope of finding possible matches. In this study, we propose a computational strategy for de novo generation of molecules with high binding affinities to the specified target and other desirable properties for druglike molecules using reinforcement learning. A deep generative model built using a stack-augmented recurrent neural network initially trained to generate druglike molecules is optimized using reinforcement learning to start generating molecules with desirable properties like LogP, quantitative estimate of drug likeliness, topological polar surface area, and hydration free energy along with the binding affinity. For multiobjective optimization, we have devised a novel strategy in which the property being used to calculate the reward is changed periodically. In comparison to the conventional approach of taking a weighted sum of all rewards, this strategy shows an enhanced ability to generate a significantly higher number of molecules with desirable properties.