Neutrons and the study of macromolecular structures

New humidity chamber - video teaser New humidity chamber - video teaser

Watch Dirk Wallacher and Matthew Barrett on the new humidity chamber that will shed light on processes behind Alzheimer’s disease!

The human genome is believed to code for between 40,000 and 1000,000 proteins. In the current, post-genomic era, information resulting from genetic sequencing is being harnessed to reveal how these proteins are involved in complex cellular processes. Each protein does a particular job and to really understand life´s processes we must find out how all of them perform their role. We know that the shape and structure (the arrangements of atoms) of proteins is related to their function, and we are starting to realise that dynamic changes within a molecular structure might also be involved.

This is particularly important to treat illness, for example, as most diseases result from a malfunction at the molecular level – a structural defect resulting in an inactive enzyme, a pathogen blocking a crucial cellular process.

In recent years, neutron scattering has played an increasing role in the study of biological structures.

Neutron scattering methods

In biology, the main objects of study are large molecules such as nucleic acids, proteins, lipids or complex sugars such as carbohydrates, with sizes ranging from 1 to 10 nanometres.

The wavelength of neutrons makes them ideal to study such large molecules, or even macromolecular structures such as cell membranes or viruses.

In particular, small angle neutron scattering (SANS), which involves scattering neutrons at very small angles can be used to study complexes of several molecules.

Hydrogen bonds Hydrogen bonds Example for backbone hydrogen bonds in an alpha-helix of myoglobin showing the different exchange behaviour (hydrogen to deuterium) of the amid hydrogen atoms. Left side: fully exchanged amid hydrogen atom. Right side:Example of an amid hydrogen atom with a low degree of exchange. The contour maps are shown in blue for a positive contour level (indicating deuterium, carbon, oxygen and nitrogen) and in red for a negative contour level (indicating hydrogen 1H). - Picture Andreas Östermann FRMII/TUM

Hydrogen bonds in in an alpha-helix of myoglobin revealed by neutron diffraction

Another important characteristic of neutrons is their scattering power. Neutrons scatter off different atoms with different power, which allows us to see inside molecules.

A technique called contrast variation allows to highlight parts of a structure by replacing its hydrogen atoms with the stronger-scattering deuterium (a hydrogen isotope containing a neutron in its nucleus).

Another interesting characteristic of neutrons is that they can lose or gain energy to or from the atom they bounce against during scattering. This phenomenon, called inelastic scattering will set the atoms in motion, and can therefore reveal their motion patterns. This can be used to determine how a molecule moves and if it has flexible or rigid parts.

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