|The Protein Problem
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
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?