London

Discerning the shape and structure of biomolecules is a sizeable problem — huge, complicated structures such as proteins are among the toughest molecules to analyse. Three researchers who developed key tools to study these giants have been rewarded with the Nobel Prize in Chemistry.

Half of the prize goes to Kurt Wüthrich of the Swiss Federal Institute of Technology in Zürich and the Scripps Research Institute in California, for finding ways to determine the three-dimensional structures of large biological molecules using nuclear magnetic resonance (NMR) spectroscopy .

John Fenn of the Virginia Commonwealth University in Richmond and Koichi Tanaka of the Shimadzu Corporation in Kyoto share the other half for inventing techniques to identify and analyse proteins and other large structures using mass spectrometry. At 43, Tanaka is the youngest chemistry laureate since 1967, and the second Japanese scientist to receive a Nobel this year, following physics winner Masatoshi Koshiba.

“The possibility of analysing proteins in detail has led to increased understanding of the processes of life,” says the Nobel Foundation. “Researchers can now rapidly and simply reveal what different proteins a sample contains and also determine what protein molecules look like in solution.”

Chemists have used NMR and mass spectrometry for decades to study small molecules. But the large size and complex structure of proteins posed problems for biologists wanting to do the same.

NMR analyses the way a molecule's atoms absorb radio waves in a powerful magnetic field. Proteins can contain thousands of atoms, so they give highly confusing NMR spectra. But in the 1980s, Wüthrich showed that NMR is possible for proteins. He invented 'sequential assignment' in which he determined the distance between any two hydrogen atoms in the molecule. He could then pair each peak of radio absorption with a hydrogen nucleus in the protein. This allowed the structure of proteins to be determined in the form in which they exist in the body — in solution — rather than as crystals.

Mass spectrometry is a highly sensitive analytical tool that separates molecules according to their size. Fenn and Tanaka found ways of turning proteins into a charged vapour, to be accelerated by an electric field and detected in a mass spectrometer.

Tanaka's technique — soft laser desorption — uses a laser pulse to blast material from solid or viscous biological samples. Fenn developed a different approach, electrospray ionization, which creates a fine spray from a protein solution using an electric field.

Fenn has “been in a total state of shock” since being given the news in a dawn phone call on 9 October. “It's like being struck by lightning,” he says. “You know it happens to some people but the odds are so great you never believe it will happen to you.”