Deep generative molecular design and its value in modern drug discovery

Abstract

IntroductionDeep generative models are reshaping de novo drug design by enabling creation of novel, property-optimized molecules beyond traditional chemical libraries. Advances in deep learning, molecular representation learning, and structure-aware modeling now enable algorithms to propose molecules that satisfy complex pharmacological constraints, accelerating hit identification.Areas coveredThis review outlines recent advances in generative molecular design, including neural network-based frameworks, reinforcement learning systems, diffusion models, and language model-based transformers. The authors outline how each class generates and optimizes molecular structures and review generative AI's practical applications in drug discovery, illustrating translational progress. Current bottlenecks are critically analyzed alongside emerging solutions. This review is based on a systematic literature search conducted in Google Scholar and PubMed, covering studies published up to December 2025.Expert opinionGenerative AI's greatest promise lies not in generating more molecules, but in generating better hypotheses, structures that are synthetically accessible, biologically plausible, optimized across potency, selectivity, and pharmacokinetics. The next phase will be led by multimodal foundation models capable of reasoning jointly about chemistry, protein structure, and cellular response, supported by automated synthesis and high-throughput experimentation. As these components are integrated, generative molecular design will guide lead optimization and reshape how new therapies are discovered and developed.