The inspiration that X-rays could reveal the structures of chemical compounds inevitably gave way to the perspiration required to solve more and more complicated structures. Max Perutz and John Kendrew received the Nobel Prize in Chemistry in 1962 for their major achievement of successfully using X-rays to determine the structures of complex proteins.
The pattern of regularly spaced dots produced by passing X-rays through crystals is the result of a complex series of reflections and interactions that occur as the X-ray waves bounce off each atom in the crystal. In the early days of X-ray crystallography, when researchers mainly worked on simpler compounds containing tens of atoms, the positions of atoms in these molecules could be derived from their X-ray patterns using trial-and-error calculations and informed intuition. However, using the same methods in complex molecules such as proteins, which contain thousands of atoms, proved to be a futile task. The number of reflections and interactions within these crystals becomes so complex that to translate X-ray patterns into molecular structures also requires knowledge about which particular point in the cycle of waves – known as the phase – these X-ray waves are at when they form each dot.
Perutz overcame this phase problem by incorporating heavy atoms, namely those of mercury, into specific positions in a protein molecule, without affecting the positions of the other atoms. These heavy atoms alter the intensities of the diffraction pattern in such a way that researchers can pinpoint the precise positions of these atoms by comparing this new pattern of dots with the original one. Knowing where the heavy atoms are located in an X-ray pattern provides the reference points researchers need to calculate the missing phase information of the reflected X-rays.
Using this method Perutz determined the molecular structure of the protein haemoglobin that transports oxygen in the blood, and Kendrew, his colleague at Cambridge University, determined the molecular structure of the smaller, related protein myoglobin. This was no straighforward task. Finding the structure of myoglobin required the measurement of around 250,000 X-ray reflections on 110 crystals – a real feat of perseverance and patience.
Their work and discoveries range from cancer therapy and laser physics to developing proteins that can solve humankind’s chemical problems. The work of the 2018 Nobel Laureates also included combating war crimes, as well as integrating innovation and climate with economic growth. Find out more.