PHOTOGRAPIC: HIV Antibody moving towards a molecule.

Biological molecules are the machinery of life. Each year hundreds of scientists come to SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) to investigate the structures of proteins, nucleic acids and other important molecules and study viruses, microbes and cells.

Macromolecular crystallography, the primary technique used to study the building blocks that make up living organisms, is one of the most active areas of research at SLAC. These studies increase our understanding of human disease – exposing, for instance, how genetic mutations may cause diabetes – and have contributed to the development of drugs used to treat influenza, late-stage melanoma, HIV infection and other ailments.

To determine the structure of a biological molecule, scientists first grow a crystal, usually no bigger than a grain of salt, which contains many copies of the molecule ordered into a regular pattern. The crystallized sample is then exposed to a thin beam of intense, highly focused X-rays created by SSRL's synchrotron ring. X-rays scatter off atoms in the sample and form a unique pattern of spots on a detector. Scientists use that pattern to work out the structure of the molecule, atom by atom.

The SSRL was one of the first synchrotron light sources to carry out macromolecular crystallography experiments. Experiments here earned Stanford University’s Roger Kornberg the 2006 Nobel Prize in Chemistry. He and his colleagues used macromolecular crystallography to solve the structure of RNA polymerase, which contains more than 30,000 individual atoms. RNA polymerase plays a key role in how information stored in DNA is translated into the proteins of life.

The Linac Coherent Light Source (LCLS) at SLAC is revolutionizing macromolecular crystallography by allowing scientists to determine the structures of biological molecules that resist forming large crystals. Instead, researchers convert them into tiny “nanocrystals” for analysis in the X-ray laser beam. This technique is opening a new path for studying important proteins, including those that play key roles in disease and its treatment and large protein complexes involved in photosynthesis.

Other LCLS experiments are making “snapshots” of individual viruses and microbes, with the goal of some day compiling those images into 3-D reconstructions and stop-action movies.