Linus Pauling and the use of physical models in investigating the structure of molecules

From Algis Valiunas on Linus Pualing in The New Atlantis:

By the early 1950s Pauling had been stalking the secret of life for a good long time. Ever since his early work on hemoglobin in the 1930s he had been thinking “more generally about the properties of the large molecules found in living organisms and about the problem of the structure of proteins,” as Pauling recalled to Judson. English crystallographers were publishing amino acid studies without descriptions of structure and with X-ray diffraction reports that misinterpreted the structural patterns they recorded. Molecular biologist William Astbury believed that he had discovered the precise fit of DNA and protein in the chromosome, but Pauling’s own measurements of bond lengths and angles in simple molecules told him Astbury was wrong about the spacing of repetitions in the coils of molecular structure. Pauling and his Caltech colleague Robert Corey labored from 1937 until 1948 to nail down numerous amino acid and peptide structures in order to convince themselves that the earlier work with simpler molecules hadn’t led them astray. Confirmed in their basic suppositions, Pauling and Corey began constructing models out of wood, metal, and plastic to render the exact helical coils of the polypeptide chain that formed the protein. These were, as Judson writes,

precisely scaled physical representations of the atoms — open three-dimensional puzzles in which the individual pieces to be fitted together already carried many of the limitations of angles, lengths, and sizes. These simple toys were one of Pauling’s most remarkable contributions to molecular biology: they amounted to a kind of analogue computer that embodied many of the physical rules and restrictions, in order to cut out the endless refiguring of interlocking readjustments.

Pauling recollected in his 1954 Nobel Prize lecture that these models were conceived of necessity; “extensive numerical calculations” were the only alternative, and for exceedingly complex structures these were simply impossible. The models themselves had to be fabricated with great care; even very slight errors of angle or size would make them useless.

Working from their models, Pauling and Corey (joined sometimes by another former Caltech colleague, Herman Branson) published a series of articles in 1950 and 1951 describing proposed structures for hemoglobin and various other proteins found in substances ranging from hair to muscle to feathers. Their rivals at the Cavendish blazed with envy at Pauling’s genius.

Of course, the Cavendish folks (Watson and Crick) got DNA right while Pauling got it wrong. Note, however, that Pauling, who was trained as a chemist, did get two solo Nobel Prizes, the only one ever to do so. 

Nevertheless, as Judson writes, “The discovery of the structure of DNA by James Watson and Francis Crick was itself a tribute — Crick’s tribute — to Linus Pauling.” Pauling and his molecular models pointed the way in, although he failed to understand just what he saw when he drew near to the mystery.

H/t 3QD.