Generative Flow Networks for Lead Optimization in Drug Design (Student Abstract)

Abstract

This paper investigates the application of Generative Flow Networks (GFlowNets) to lead optimization in drug discovery. GFlowNets provide a novel framework for generating diverse molecular structures while optimizing for desired properties, addressing the limitations of traditional methods in exploring vast chemical spaces. We adapt GFlowNets to incrementally modify lead compounds, integrating domain-specific heuristics to guide the generation process. Our method employs the trajectory balance objective on a graph neural network (GNN), to learn a policy that samples fragments based on a multi-objective reward. The reward function ensures increase in cell permeability and similarity to the starting molecule. The results on benchmark datasets of activity cliffs demonstrate that GFlowNets can generate diverse modifications, producing optimized candidate molecules with improvement in cell permeability. This work can be extended with other pharmacokinetic properties for lead optimization in early-stage drug development, potentially accelerating the discovery of novel therapeutics.