Computer-aided structural modeling and drug discovery for G-protein-coupled receptors in the age of artificial intelligence

G-protein-coupled receptors (GPCRs) are a large family of membrane proteins that mediate cellular responses to diverse stimuli and serve as targets for ∼35 % of Food and Drug Administration–approved drugs. Their structural complexity, conformational heterogeneity, and membrane embedding have historically hindered experimental characterization, although advances in crystallization and cryogenic electron microscopy have expanded access to high-resolution receptor structures. In parallel, artificial intelligence (AI) has transformed protein modeling and drug discovery as recognized by the 2024 Nobel Prize in Chemistry. This minireview highlights recent applications of AI to GPCR research (2023–2025), including structure prediction, virtual screening, generative design of small molecules and protein binders, mechanistic studies using molecular dynamics, and systems-level analyses. Together, these approaches are reshaping GPCR biology and accelerating next-generation drug discovery. Overview of Contemporary AI usage toward GPCR Modeling. AI usage in GPCR modeling spans diverse applications. Those applications which are addressed in this minireview include: Structure Prediction, Systems Biology, de novo Drug Design, Mechanistic Modeling, and Virtual Screening.