Abstract

Exactly a hundred years ago, the Philosophical Society published a paper by Lawrence Bragg describing his law on the diffraction of x-rays by crystals. That work set in motion a remarkable cascade of events in chemistry. In the previous hundred years, chemists, by sheer imagination and ingenuity had not only discovered the existence of molecules but had very concrete ideas about their structure. But Bragg’s law made it possible to directly determine the structures of molecules from x-ray diffraction measurements, so for the first time, molecules could be “seen.” This led initially to the three-dimensional structures of simple molecules like common salt, to increasingly more complex ones like vitamins and antibiotics. Another major advance in the method was made by Max Perutz, himself a protegé of Bragg, which allowed the determination of the structures of molecules such as proteins with thousands of atoms.

In this talk, I shall allude briefly to the history of the field, and then describe how the method in its current state was used to solve the structure of the ribosome, the large molecular machine that consists of half a million atoms and is present in all forms of life. The ribosome reads the sequence of information in our genes to synthesize the proteins encoded by them. The atomic structure of the ribosome has yielded insights into its function and its ancient origins from a world that existed before proteins or DNA . Finally, because ribosomes are so ancient, they have diverged significantly between humans and bacteria. As a result, a large number of useful antibiotics work by blocking the bacterial ribosome without affecting the human version. The atomic structures allow us to see how these antibiotics inhibit the ribosome, and pave the way for the design of new antibiotics that can overcome resistant strains.