X-ray crystallography and the first protein structure (1958)
John Kendrew and Max Perutz at Cambridge used X-ray crystallography to determine the three-dimensional structure of myoglobin, a protein that stores oxygen in muscle tissue. The work required growing protein crystals, bombarding them with X-rays, and painstakingly interpreting the resulting diffraction patterns. It took Kendrew roughly two decades of effort.
Kendrew and Perutz received the 1962 Nobel Prize in Chemistry. X-ray crystallography became the dominant method for determining protein structures for the next six decades.
By 2020, researchers had determined approximately 170,000 protein structures through experimental methods. That number represented a tiny fraction of the estimated 200 million known proteins, illustrating the bottleneck that AlphaFold ultimately broke.
The contrast in scale is the point. What took Kendrew 20 years for a single protein, AlphaFold 4 now accomplishes for multi-protein complexes in minutes. The roughly 170,000 experimentally determined structures over six decades compare to 214 million computationally predicted structures released in a single database expansion.