Electron Density Redistribution Accounts for Half the Cooperativity of α Helix Formation

The energy of α helix formation is well known to be highly cooperative, but the origin and relative importance
of the contributions to helical cooperativity have been unclear. Here we separate the energy of helix formation
into short range and long range components by using two series of helical dimers of variable length. In one
dimer series two monomeric helices interact by forming hydrogen bonds, while in the other they are coupled
only through long range, primarily electrostatic interactions. Using Density Functional Theory, we find that
approximately half of the cooperativity of helix formation is due to electrostatic interactions between residues,
while the other half is due to nonadditive many-body effects brought about by redistribution of electron
density with helix length.