The impressive achievements of structural biology leave us in awe, but also raise the question of whether we can still expect major developments in the field in the future. Before I provide my answer to this question, let me briefly reflect on the major advances in structural biology over the past three decades.

Thirty years ago, in 1994, the journal Nature Structural Biology (renamed Nature Structural and Molecular Biology ten years later) was launched as a response to the rapid growth of the field¹. Around that time, I started as a graduate student at EMBL Grenoble and witnessed these exciting developments firsthand. The rapid growth in structural biology in the 1990s was due to several technological advances in X-ray crystallography, which enabled many structural studies of biomolecules. First, cryopreservation of crystals prevented radiation damage of proteins and thereby enabled the collection of complete diffraction data sets from single crystals². Second, next-generation X-ray sources became available, in particular the European Synchrotron Radiation Facility next door to us, providing the brightest source of X-rays at that time³. Third, X-ray detectors made the tedious recording of diffraction patterns on film obsolete. Fourth, phasing of diffraction data became more straightforward by incorporating selenomethionine into proteins and using anomalous scattering⁴. Finally, faster computers enabled more-rapid data processing, and improvements in computer graphics and software facilitated the building and refinement of atomic models.

结构生物学取得的令人瞩目的成就让我们惊叹不已，但也提出了一个问题：我们是否仍然可以期待该领域未来的重大发展。在回答这个问题之前，让我简要回顾一下过去三十年来结构生物学的主要进展。

三十年前的 1994 年，《自然结构生物学》杂志（十年后更名为《自然结构与分子生物学》）创刊，作为对该领域快速发展的回应¹。大约在那个时候，我开始在格勒诺布尔 EMBL 攻读研究生，并亲眼目睹了这些令人兴奋的发展。结构生物学在 20 世纪 90 年代的快速发展得益于 X 射线晶体学的多项技术进步，这使得许多生物分子的结构研究成为可能。首先，晶体的冷冻保存可以防止蛋白质受到辐射损伤，从而能够从单晶体中收集完整的衍射数据集²。其次，下一代 X 射线源出现，特别是我们隔壁的欧洲同步辐射设施，提供了当时最亮的 X 射线源³。第三，X射线探测器使得在胶片上记录衍射图样的繁琐过程成为过去。^{第四，通过将硒代蛋氨酸掺入蛋白质并使用反常散射4 ，}衍射数据的定相变得更加简单。最后，更快的计算机实现了更快速的数据处理，计算机图形和软件的改进促进了原子模型的构建和完善。