The failure of Pauling's and Corey's 1953 model for the structure of DNA was more than humiliating. It was a public demonstration of the limits of Pauling's
model-building approach. By relying on a minimal number of facts, some hasty calculations,
and his own unparalleled intuition, Pauling came up with a triple-chain structure
that was not only chemically suspect and structurally unlikely, but did not say anything
about how DNA might function as the carrier of genetic information. After its publication
(and swift rejection), Pauling seemed to lose his taste for taking on more biomolecular
theoretical structures. After winning the 1954 Nobel Prize in chemistry for his work
on the chemical bond he assumed the role of elder statesman of science, overseeing
the work of others, creating textbooks, writing review articles, and spending increasing
amounts of time on peace work. Although he continued to publish papers on protein
structures through 1955, it was mostly clean-up work. By then the important advances
were being made elsewhere - especially in England, where the Cavendish group's long
trek toward solving the structures of globular proteins finally began to yield important
results.
Frederick Sanger, after eight years of tedious work, published the full amino acid
sequence of insulin in 1953 (an achievement that won him a Nobel Prize in 1958). John
Kendrew, working with Perutz under Bragg's general direction, published a first, fuzzy
look at the full structure of the myoglobin molecule in 1958, then sharpened it into
a high-resolution representation in 1960. By then Perutz had also achieved success,
publishing the first detailed structural description of hemoglobin. The two men shared
a Nobel Prize in 1962.
It was then that the limits of Pauling's alpha helix became clear. Myoglobin and hemoglobin
were not what anyone expected. There was no apparent regularity there. These were
lumpy, meandering, misshapen-looking tangles of protein. There were sections of alpha
helix, especially in myoglobin, but where was the tight crystalline-like packing of
alpha-helix chains that some people (including Pauling) had expected? As Kendrew put
it in his description of myoglobin, "Perhaps the most remarkable features of the molecule
are its complexity and its lack of symmetry. The arrangement seems to be almost totally
lacking in the kind of regularities which one instinctively anticipates, and it is
more complicated than has been predicted by any theory of protein structure."
After the publication of the myoglobin and hemoglobin structures, Pauling's alpha
helix began to look like a connecting rod, a way to get a polypeptide chain from point
A to point B. It did not appear to contribute in any direct way to the molecules'
function. As more complicated globular proteins were solved through the 1960s and
1970s, it appeared that fully functional proteins involved not one, but three or four
levels of structure: primary (Sanger's sequence of amino acids); secondary (relatively
simple default forms assumed by polypeptide chains, like the alpha helix); tertiary
(the ways secondary structures in a single chain were twisted and folded into more
complex shapes); and in some cases quaternary structures (the clustering of several
chains into a complete protein; hemoglobin, for instance, has four chains). Pauling
had emphasized the importance of hydrogen bonds in holding proteins together, but
as more was learned it became clear that a number of other forces – especially hydrophobic
factors – played an even bigger role in functional molecules.
The alpha helix and pleated sheets were not really functional proteins at all. They
were parts from which functional proteins were made. They were secondary structures.
|