First principles predictions of the preferences for secondary structure

Changmoon Park+ and William A. Goddard III*

Materials and Process Simulation Center, Beckman Institute (139-74)

Division of Chemistry and Chemical Engineering

California Institute of Technology, Pasadena, California 91125

Abstract

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 carboxy terminus of a poly-alanine alpha-helix as a function of helix length N. We find that for N ³ 4 there is a strong preference for the new residue to adopt an alpha-helix conformation. Using charges from the QM calculations, we carried out MD calculations which show that the QM effects are dominated by electrostatic interactions. This dipole-dipole stabilization increases with the length of alpha-helix, making alpha-helix formation a cooperative process.

The roles of charged residues are also explained: stabilizing or destabilizing alpha-helices depending on their positions in alpha-helices. These results provide insight into the conformational preferences and kinetics of protein folding.