Linus Pauling and the Structure of Proteins: A Documentary History Narrative  
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The Protein Problem
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The 1940s turned into the 1950s, and still there was still no definitive answer to the basic question: What is the structure of a protein? A lot had happened, of course, and a great deal had been learned since Pauling began his work in the 1930s. It was becoming very clear that proteins were made from long chains of amino acids, as Pauling and others had long said. Pauling's work on denaturation and the importance of the hydrogen bond had also had an effect. More and more researchers were coming to believe that polypeptide chains were folded into precise shapes that were held in place with hydrogen bonds. Proteins were being broken apart and the pieces analyzed chemically, creating, bit by bit, an amino acid map of at least some of the thousands of known proteins molecules.

But still no one had come up with a detailed, accurate, provable structure. The British, using a top-down approach that started with the x-ray analysis of whole proteins, had been beavering away for years seemingly without coming up with much. A sort of fatigue was setting in, at least according to this recollection by Max Perutz, who had been trying to solve the hemoglobin structure by analyzing the x-ray patterns of the complicated molecule, and who found himself worrying about "the stark truth that the years of tedious labor, the many nights of interrupted sleep and the appalling strain of measuring the intensities of thousands of little black spots by eye had brought me no nearer to the solution of the structure of hemoglobin, and that I wasted some of the best years of my life trying to solve a seemingly insoluble problem."

Pauling had avoided the British approach in favor of a bottom-up attack on proteins, using detailed information on the precise structure of amino acids and small peptides (protein fragments) as a basis for thinking about models of protein structure that might fit what was known about their chemistry and activity. When he returned home, he had followed up by assigning a visiting professor of physics, Herman Branson, to review all possible spiral protein models that accommodated his restrictions – a planar peptide bond, maximum hydrogen bonding – to see if there were other possible helixes that he had missed. Branson used his keen grasp of mathematics and very accurate model-building equipment to construct dozens of variations. In 1949 he presented the results to Pauling: There were only two stable helixes that reasonably fit the known sizes of amino acids, obeyed the laws of chemistry, and accommodated Pauling's restrictions. Most disappointing was the fact that neither of them showed any sign of the 510-picometer repeat that Astbury's studies had said should be there. The tighter of the two spirals came close, at 540 picometers, but the difference was enough to give Pauling pause. "I felt so strongly that the structure must explain the X-ray data that I took a chance by waiting," he later said.

That was where things stood when Pauling picked up a spring 1950 issue of the Proceedings of the Royal Society and read a long paper by Sir Lawrence Bragg, John Kendrew, and Max Perutz, titled "Polypeptide Chain Configurations in Crystalline Proteins."

Had the British beaten him to the prize?

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See Also: Linus Pauling note to self concerning research on succinic dehydrogenase. April 12, 1950. 
See Also: Linus Pauling note to self concerning the configurations of stable states of proteins. October 10, 1950. 

Click images to enlarge 

Herman Branson. 1970s.

Page 2
Notes re: values for interatomic distances in collagen molecules, 1950s.

"What I'm telling you now is that I was thinking of the alpha helix in hemoglobin, and I refrained from saying anything to Max, not because I wanted to keep him from having significant information, but because there's no use disturbing people about something unless you feel happy with it yourself."

Linus Pauling
December 23, 1975
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