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Insulin and heavy atoms


The phase problem
Dorothy Hodgkin Scientist
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[Q] Now what was the big problem, Dorothy, getting into protein structure solution?

It was to find how to solve the phase problem and actually, the... there was only one method known in the 1930s in which the phase problem could be solved which was by isomorphous replacement. And that in fact is if you're being strictly honest, you date back to a paper by Duane in the American Academy in 1925 or '26 which the first electron density maps are calculated by a formula of course proposed by WH Bragg. But in 1915 when nobody had done it until 1926, curiously enough, and they point out having looked at and seeing what was happening with their figures, that in fact... well assuming they knew the structure in their calculation, they didn't need to know it, that all the signs were determined by the heavy atoms, the heaviest atom present, which was the chloride of sodium chloride. And they also pointed out that alternatively, we would have found it by comparing the signs for sodium chloride and potassium chloride but somehow nobody saw that immediately, so Bragg himself did his first electron density maps with signs calculated from the positions he'd already found from the atoms and dioxide and so on. And Henry Lipson says how they suddenly realised that in fact all these signs were determined by the calcium in the structure.


British pioneer of X-ray crystallography, Dorothy Hodgkin (1910-1994), is best known for her ground-breaking discovery of the structures of penicillin, insulin and vitamin B12. At age 18, she started studying chemistry at Somerville College, Oxford, then one of the University of Oxford colleges for women only. She also studied at the University of Cambridge under John Desmond Bernal, where she became aware of the potential of X-ray crystallography to determine the structure of proteins. Together with Sydney Brenner, Jack Dunitz, Leslie Orgel, and Beryl Oughton, she was one of the first people in April 1953 to see the model of the structure of DNA, constructed by Francis Crick and James Watson. She was awarded the 1964 Nobel Prize in Chemistry and is also known for her peace work with organisations such as Science for Peace and the Medical Aid Committee for Vietnam. All recorded material copyright of The Biochemical Society.

Listeners: Guy Dodson

Guy Dodson studied chemistry and physical science at the University of New Zealand, followed by a PhD on the crystallographic study of an alkaloid. In 1961, he came to Oxford to work on the crystal structure of insulin. In the mid 1970s Guy and his wife moved to York University to establish a laboratory. In addition to insulin studies the laboratory has investigated many complex molecules of medical significance, including haemoglobin, myoglobin, HIV related proteins, proteases and proteins involved in managing nucleic acids in cells. In 1993, he went to the NIMR in London to establish a crystallographic group in an environment that spanned molecular, physiological and disease-related disciplines. Here his research began on some cell signalling proteins. His interests on medically relevant proteins included prions, malarial and TB proteins, and some clinically relevant thrombin inhibitors. Guy Dodson retired in 2004 but is still finding much to do in York and the NIMR.

Tags: WH Bragg

Duration: 2 minutes, 12 seconds

Date story recorded: 1990

Date story went live: 02 June 2008