Multi-constraint molecular generation based on conditional transformer, knowledge distillation and reinforcement learning

Machine learning-based generative models can generate novel molecules with desirable physiochemical and pharmacological properties from scratch. Many excellent generative models have been proposed, but multi-objective optimizations in molecular generative tasks are still quite challenging for most existing models. Here we proposed the multi-constraint molecular generation (MCMG) approach that can satisfy multiple constraints by combining conditional transformer and reinforcement learning algorithms through knowledge distillation. A conditional transformer was used to train a molecular generative model by efficiently learning and incorporating the structure-property relations into a biased generative process. A knowledge distillation model was then employed to reduce the model's complexity so that it can be efficiently fine-tuned by reinforcement learning and enhance the structural diversity of the generated molecules. As demonstrated by a set of comprehensive benchmarks, MCMG is a highly effective approach to traverse large and complex chemical space in search of novel compounds that satisfy multiple property constraints. Combining generative models and reinforcement learning has become a promising direction for computational drug design, but it is challenging to train an efficient model that produces candidate molecules with high diversity. Jike Wang and colleagues present a method, using knowledge distillation, to condense a conditional transformer model to make it usable in reinforcement learning while still generating diverse molecules that optimize multiple molecular properties.

Automated summary

The MCMG approach combines a conditional transformer and reinforcement learning algorithms through knowledge distillation to generate molecules that satisfy multiple constraints, providing an efficient way to traverse large and complex chemical space in search of novel compounds.