Reinforced Active Learning for Large-Scale Virtual Screening with Learnable Policy Model

Yicong Chen, Jiahua Rao, Jiancong Xie, Dahao Xu, Zhen WANG, Yuedong Yang

Keywords: Virtual Screening, Active Learning, Molecular Activity, Drug Discovery

TL;DR: We present GLARE, a reinforced active learning framework that improves virtual screening efficiency by dynamically optimizing molecular selection while balancing chemical diversity, biological relevance, and computational constraints.

Abstract:

Virtual Screening (VS) is vital for drug discovery but struggles with low hit rates and high computational costs. While Active Learning (AL) has shown promise in improving the efficiency of VS, traditional methods rely on inflexible and handcrafted heuristics, limiting adaptability in complex chemical spaces, particularly in balancing molecular diversity and selection accuracy.
To overcome these challenges, we propose GLARE, a reinforced active learning framework that reformulates VS as a Markov Decision Process (MDP). Using Group Relative Policy Optimization (GRPO), GLARE dynamically balances chemical diversity, biological relevance, and computational constraints, eliminating the need for inflexible heuristics.
Experiments show GLARE outperforms state-of-the-art AL methods, with a 64.8% average improvement in Enrichment Factors (EF). Additionally, GLARE enhances the performance of VS foundation models like DrugCLIP, achieving up to an 8-fold improvement in EF$_{0.5\\%}$ with as few as 15 active molecules. These results highlight the transformative potential of GLARE for adaptive and efficient drug discovery.

Primary Area: Neuroscience and cognitive science (e.g., neural coding, brain-computer interfaces)

Submission Number: 2778