title: Simulation of an all-beta 3-icosapeptide containing the 20 proteinogenic side chains: effect of temperature, pH, counterions, solvent, and force field on helix stability.
abstract: Simulations of various beta-peptides have in the last years clarified several issues concerning peptide folding equilibria and interpretation of experimental data, especially from NMR and CD spectroscopy. These simulations involved different temperatures, pH-values, ionic strengths, solvents, and force-field parameters, but a variation of these factors for one beta-peptide has not yet been done. To investigate the influence of varying these factors, we analyze the helix stability of an all-beta3-icosapeptide bearing all 20 proteinogenic amino acid side chains, which is experimentally observed to fold into a 3(14)-helix in methanol but not in water. Structural aspects, such as hydrogen-bonded rings and salt bridges, are discussed and a comparison with NMR primary (NOE distance bounds and 3J-values) and secondary (NMR derived model structures) data is made. We further investigate the reasons for the 3(14)-helix stability/instability in methanol/water. Of all factors studied, the presence of counterions seems to be the one inducing most significant effects in the simulations.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH, CH-8093 Zürich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Trzesniak
authors.forename: Bernhard
authors.initials: B
authors.lastname: Jaun
authors.forename: Raveendra I
authors.initials: RI
authors.lastname: Mathad
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012997:Solvents; D013696:Temperature
chemical_list: D010455:Peptides; D012997:Solvents