The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain
Fold a protein chain by the rules of the chemical bond, and one shape falls out: the α-helix.
Before anyone had ever seen a protein clearly, Linus Pauling folded one in his head — using nothing but the rules of the chemical bond.
The big idea
Proteins are long chains of amino acids, and to work they must fold into precise shapes. In 1951 Pauling and his colleagues asked a daring question: what shapes can the chain take if you obey, exactly, the rules chemistry already knew — how long each bond is, how stiff each link is, and where the tiny attractions called hydrogen bonds can form? The answer was almost forced. One especially neat shape kept appearing: a right-handed coil, like a spiral staircase, which they named the α-helix. Each turn of the coil is stitched to the next by hydrogen bonds, which makes it sturdy and self-supporting.
How it came about
Pauling had the crucial clue years earlier: the link between two amino acids — the peptide bond — is flat and rigid, not free to twist, because of the way its electrons are shared. With the exact shapes of amino acids measured in his Caltech lab by Robert Corey, and the geometry worked out in detail by the physicist Herman Branson, Pauling looked for coils in which every hydrogen bond came out straight and the right length.
A rival team in Cambridge had searched the year before and failed, because they had assumed each turn must hold a whole number of amino acids. Pauling let go of that assumption — his helix has about three and a half per turn — and the structure clicked into place. He is said to have worked part of it out while ill in bed, folding a paper chain by hand until the bonds met.
Why it mattered
It was the first time anyone had correctly predicted a piece of a protein's shape, and it was confirmed almost at once when Max Perutz spotted exactly the X-ray signal the α-helix demanded. It showed that the shapes of life's molecules follow from plain chemistry — and it pioneered the model-building method that, just two years later, cracked the structure of DNA.
A way to picture it
Think of a spiral staircase made of paper links, where a point on the rail sits directly above the matching point one turn below. Now imagine tiny magnets that only click when two links sit squarely above each other, four steps apart. The only way to build the staircase so every magnet clicks is to give each turn about three and a half steps — not three, not four. Those magnets are the hydrogen bonds, and that clicked-together staircase is the α-helix. Once it is zipped up the whole length, it holds its own shape.
Where it sits
Pauling's α-helix and his model-building style directly shaped the DNA double helix two years later (see watson-crick-1953); both are right-handed coils held together by hydrogen bonds. The α-helix is one of the basic alphabet-letters of protein shape — and predicting how a chain of amino acids arranges those letters into a whole fold is exactly the problem that AlphaFold (see alphafold-2021) finally solved seventy years on.