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.

Keywords:

• polarizable model
• methanol solvent model
• peptide folding
• β-peptide

Acknowledgements

The author would like to thank Xavier Daura for making available the simulations he had carried out on the β-pepides dealt with in this report. This work was financially supported by the National Center of Competence in Research (NCCR) in Structural Biology and by grant number 200020-121913 of the Swiss National Science Foundation, by grant number 228076 of the European Research Council (ERC), and by grants number IZLCZ2-123884 (Swiss) and GJHZ0906 (Chinese) of the Sino-Swiss Science and Technology Cooperation Program, which is gratefully acknowledged.

Supporting Information: A study of the number of clusters as the function of time and the specification of the NOE atom pairs and ³ J-coupling constants and the detailed results for the three peptides are available in supporting information.