F.A.D.E. (Fully Agentic Drug Engine): A Conversational AI Platform for Drug Discovery

Abstract

Drug discovery remains one of the costliest and most time-intensive endeavors in the pharmaceutical pipeline, with average development costs exceeding $2.3 billion per drug, timelines spanning more than a decade, and attrition rates above 90% in clinical trials. While computational methods have expanded the searchable chemical space, current pipelines remain fragmented and largely inaccessible to researchers without deep interdisciplinary expertise. Here we present F.A.D.E. (Fully Agentic Drug Engine), a multi-agent, open-source platform that converts natural language queries into potential drug candidates, substantially lowering the expertise barrier to advanced computational drug discovery. F.A.D.E. employs a three-branch hierarchical architecture that adapts to the level of available structural data for any protein target, integrating structure prediction, binding pocket detection, equivariant diffusion-based de novo ligand generation, and binding affinity estimation into a single automated pipeline. We validate F.A.D.E. on two structurally distinct targets: the epidermal growth factor receptor kinase domain (EGFR), a well-established oncology target, and cellular retinol-binding protein 1 (CRBP1), a lipid-binding protein involved in retinoid metabolism. For EGFR, our generated candidates achieved QED scores of 0.85 compared to 0.46 for the co-crystallised reference ligand, demonstrating marked improvement in predicted drug-likeness. Results across both targets confirm that F.A.D.E. can reliably generate chemically tractable, drug-like hit compounds across diverse protein classes from simple natural language input.