García-Reyes Rubén A, Massó Quiñones Laura N, Ruy Hajin, Castro Daniel C
Biophotonics Research Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110 USA.
Roy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO 63110 USA.
NPP Digit Psychiatry Neurosci. 2025;3(1):16. doi: 10.1038/s44277-025-00038-9. Epub 2025 Jun 30.
The development and adoption of artificial intelligence (AI) provides moonshot opportunities to redefine how we generate treatments for neuropsychiatric disease. Despite the rapid advancement of AI across biomedical spheres, its implementation in drug discovery, proteomics, and neurobiology has been met with new and unexpected limitations. Historically, neuropharmacology research has used observational and invasive experimental approaches to identify novel therapeutics. Unfortunately, this classic approach suffers from laborious chemical synthesis and in vivo testing which ultimately leads to translational bottlenecks. With the implementation of AI, we are now able to expedite this early testing by modeling how a drug or protein complex may interact with a receptor of interest. By applying powerful, precision-based protein structure prediction tools, we can better tailor therapeutics and minimize undesired outcomes. Though promising, important caveats like predicting chirality of molecules, conformational changes upon binding, and determining downstream signaling elements remain critical roadblocks that functionally limit the efficacy of prediction software. This Perspective article will briefly discuss how AI-powered protein prediction software will impact drug development to transform neuropsychopharmacology research and therapeutics, while also providing insights into the limitations of these digital tools.
人工智能(AI)的发展与应用为重新定义我们如何研发神经精神疾病的治疗方法带来了巨大机遇。尽管AI在生物医学领域取得了快速进展,但其在药物发现、蛋白质组学和神经生物学中的应用却遇到了新的、意想不到的限制。从历史上看,神经药理学研究一直采用观察性和侵入性实验方法来确定新的治疗方法。不幸的是,这种传统方法存在化学合成繁琐和体内测试的问题,最终导致转化瓶颈。随着AI的应用,我们现在能够通过模拟药物或蛋白质复合物与感兴趣的受体之间的相互作用来加速早期测试。通过应用强大的、基于精度的蛋白质结构预测工具,我们可以更好地定制治疗方法并将不良结果降至最低。尽管前景广阔,但诸如预测分子的手性、结合时的构象变化以及确定下游信号元件等重要警告仍然是功能上限制预测软件功效的关键障碍。这篇观点文章将简要讨论人工智能驱动的蛋白质预测软件将如何影响药物开发,以改变神经精神药理学研究和治疗方法,同时也深入探讨这些数字工具的局限性。