Stabilization of r-Helices by Dipole-Dipole Interactions within r-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 R-helix as a function of helix length N. We find that extending the length of an R-helix increasingly favors the R-helix conformation for adding an additional residue, even in hydrophobic environment. Thus, R-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 R-helix formation results from dipole-dipole interaction within the R-helix. These results provide quantitative preferences and insight into the conformational preferences and kinetics of protein folding.