The effect of using a polarizable solvent model upon the folding equilibrium of different β-peptides

Abstract

Folding and unfolding of β-peptides has been studied extensively by molecular dynamics (MD) simulation in the past decade. In these simulations, a non-polarizable model for the solvent (mostly methanol) was used. This work has investigated the effect of using a polarizable methanol solvent model upon the folding equilibrium of β-peptides. Thirteen MD simulations covering a total simulation length of 1.25 µs for three differently folding β-peptides were analyzed. The agreement with experimental data was slightly improved by applying the polarizable solvent. In the polarizable solvent, helical structures, which have a large dipole moment, are stabilized, while no obvious effect was detected in the simulations of peptides that have a hairpin structure as the dominant fold. The introduction of electronic polarizability into the solvent model appears of importance to a proper description of folding equilibria if these are determined by competing solute conformations that have different dipole moments.