Structural chemistry, especially the structure of proteins, remained Pauling's principal problem to solve. As mentioned briefly
above, Pauling figured out a couple of fundamental structures for proteins while in England in 1948. In 1951 he published
with Robert B. Corey, a professor of Chemistry at Caltech, and Herman R. Branson, Chair of the Physics department at Howard
University, two possible structures for proteins. The alpha-helix had 3.7 amino acid residues per turn and the gamma-helix
had 5.1 residues per turn. Pauling and Corey followed up this initial theoretical article with several other articles that
discussed specific proteins. Thus, during the same year, Pauling and Corey published an article on globular proteins and stated
that hemoglobin most likely has the alpha-helix configuration with 3.7 residues per turn.
Although Pauling spent most of his time analyzing proteins and therefore focusing on the globin of hemoglobin, Pauling believed
that a better understanding of the heme was also necessary. Thus in 1951, he also returned to studying the structure of the
iron portion of hemoglobin with the help of Robert C. C. St. George, a postdoctoral fellow. Pauling had proposed previously,
in 1948, that the hemes might be embedded within the hemoglobin molecule, and therefore steric hindrance determined the accessibility
of the iron site. Thus, the first oxygen or carbon monoxide molecule to attach itself to the hemoglobin molecule reshaped
the macromolecule and made it easier for the other three oxygen or carbon monoxide molecules to attach to the iron in the
other three hemes. Prior to his article with St. George, Pauling had not experimentally investigated his theory. By analyzing
isocyanides with a spectrophotometer (an instrument that measures light intensity by comparing parts of a light spectrum)
Pauling and St. George experimentally substantiated Pauling's steric hindrance theory. Armed with this new structural interpretation,
St. George and Pauling suggested that steric hindrance resulting from the addition of oxygen to hemoglobin might push apart
the protein in sickle cell hemoglobin and thereby obstruct the sites at which sickle cell hemoglobin molecules bind to themselves.
Thus, steric hindrance explained why oxygen prevented sickle cell hemoglobin from converting into a crescent shape.