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The death of the artificial antibody project allowed Pauling to focus on more productive
areas of research. In 1943 he and his assistants started putting together a more detailed
picture of how, exactly, antibodies were able to stick to antigens. The results of
this careful, valuable research would shape Pauling's attitudes toward protein structure
for years to come.
By using carefully prepared synthetic antigens along with improved assaying techniques,
Pauling was able to show by the War's end that antibodies stuck to antigens not because
of typical chemical bonds (covalent or ionic) but because of shape. Antibody and antigen
came together like hand and precisely fitted glove, bringing significant areas of
their surfaces into very close contact. Their shapes were complementary. That close
contact brought into play a set of weak interactions called van der Waal's forces.
These were very weak bonds – only a fraction of the strength of a covalent chemical
bond – and were nonspecific, operating between almost any two atoms in close contact.
However, when the fit between antibody and antigen was just right, the sum of van
der Waal's interactions over many atoms (along with occasional hydrogen bonding and
the attraction of oppositely charged polar groups) was enough to bind the two together.
The key was harnessing many weak forces spread over a relatively large surface area.
But the fit had to be precise. If the complementary shaping of antibody to antigen
was off by just an atom or two, Pauling's group found, the binding force declined
significantly.
The ability of one molecule in the body to recognize another, and the creation of
specific interactions between them – the way an enzyme binds to only one substrate,
for instance, or an antibody to a specific antigen – was a central mystery in the
new field of molecular biology. Pauling's immunological work after 1943 cast much-needed
light on that mystery. The idea of complementary shapes came to dominate Pauling's
thinking about protein interactions in the body.
But he was still a long way from understanding with any degree of detail how any individual
protein might be built.
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Audio: Biological Specificity. January 17, 1983. (1:55) 
Video: The Importance of Weak Forces. February 28, 1995. (0:42) 
