Stabilization of α-helices by dipole-dipole interactions within α-helices

Including solvation effects (in the Poisson-Boltzmann continuum solvent approximation) we report ab initio quantum mechanical calculations (HF/6-31G**) on the conformational energies for adding alanine to the amino or carboxyl terminus of a polyalanine α-helix as a function of helix length N. We find that extending the length of an α-helix increasingly favors the α-helix conformation for adding an additional residue, even in hydrophobic environment. Thus, α-helix formation is a cooperative process. Using charges from the QM calculations, we find that the electrostatic energy dominates the QM results, showing that this increasing preference for a-helix formation results from dipole-dipole interaction within the α-helix. These results provide quantitative preferences and insight into the conformational preferences and kinetics of protein folding.