The Impact of Physics in Structural Biology

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Structural biology is a research area that uses physical techniques to determine the atomic structure of biological molecules such as haemoglobin, the ribosome or pathogenic viruses. It uses tools that have become more and more powerful during the last 60 years. The first protein structure, that of sperm whale myoglobin, was solved in 1960 using X-ray crystallography, a method that now produces 10,000 structures per year, all of them being deposited in the Protein Data Bank (PDB). In recent years, electron cryomicroscopy (cryoEM) of individual biological structures plunge-frozen in a thin film of amorphous ice, has developed rapidly in power and resolution, so that about 6,000 PDB depositions are now made each year for structures solved by cryoEM. Many of these cryoEM structures represent unstable or flexible assemblies whose structure cannot be determined by any other method, and almost all of them involve images collected on 300 keV state-of-the-art transmission electron cryo-microscopes.

Many of the techniques used in structural biology depend on the scattering by matter of elementary particles, which were themselves discovered by earlier physics research. X-rays were discovered by Röntgen as recently as 1895. Electrons were identified as the charged particles in cathode rays by J.J. Thomson in 1897. Neutrons were discovered by Chadwick in 1932. These different techniques visualise different aspects of the structures being examined, such as charge or electron density. Other physical techniques such as nuclear magnetic resonance (NMR) spectroscopy can also produce valuable information about the chemistry of the different atoms that make up biological structures. Together, these complementary approaches have now produced a wealth of information about hundreds of thousands of biological structures. There are now experimentally determined molecular models for more than half of the structures in biology, and bio-informatics or artificial intelligence techniques can be used to make predictions for the other half.
There are still lots of gaps in our knowledge of biological structures from both theoretical and experimental viewpoints, and physics has much to contribute.

References:

1. Henderson, R, (1995) The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules. Quart. Rev. Biophysics 28, 171-193.
2. Kuhlbrandt, W. (2014) The resolution revolution. Science 343, 1443-144.