Abstract Traditional Chinese Medicine (TCM) offers valuable therapeutic strategies for chronic and infectious diseases, yet the inherent complexity of its multi-component, multi-target formulations and synergistic effects presents substantial challenges to pharmacological mechanistic understanding. Structural pharmacology of Chinese Medicine has emerged as a transformative discipline, integrating structural biology, computational chemistry, and pharmacology to elucidate the precise mechanisms underlying TCM efficacy. This review synthesizes technological advancements that enable the characterization of synergistic mechanisms and dynamic molecular interactions in TCM. Key advancements include high-resolution structural techniques such as X-ray crystallography, cryo-electron microscopy, sophisticated computational approaches such as AI-driven predictive modeling, and advanced analytical platforms. We critically examine persistent technical hurdles, such as capturing transient binding events and modeling complex multi-component system dynamics. Finally, we outline future research trajectories to establish a predictive and adaptable scientific foundation for TCM modernization, facilitating its evidence-based global integration and application in precision medicine.
Wang et al. (Fri,) studied this question.