Salt-specific stability of short and charged alanine-based alpha-helices.
The alpha-helical stability of the short and net-charged (+/-6e) alanine-based peptides (AE)(6) and (AK)(6) in approximately 2.5 M electrolyte solution (NaCl, KCl, NaI, and KI) is investigated by 1 micros long all-atom computer simulations. While the nonspecific screening of electrostatic repulsion between the charged side chains stabilizes the compact helical configuration, a competing destabilization effect is induced by considerable binding of sodium (Na(+)) to the backbone carbonyl groups which is much weaker for potassium (K(+)). If Cl(-) is exchanged by the large anion I(-), cation binding and thus helix destabilization is increased due to osmotic effects and the binding affinity of I(-) to the hydrophobic alanine side chains, thereby dragging cations to the peptide. While the I(-) propensity to alanine is enhanced for the positively net-charged (AK)(6), the helix destabilization effect by NaI for this peptide, however, is much weaker when compared to (AE)(6) due to the (electrostatically induced) depletion of Na(+) at the peptide backbone; this, and the fact that KI is found to be a weak destabilizer too, demonstrates that I(-) alone is not responsible for denaturation but assists and amplifies cationic action. Our study exemplifies the molecular and highly synergetic mechanisms behind specific ion-induced (de)stabilization of protein secondary structures and its sensitive dependence on local peptide net charge and sign of charge.
Dzubiella
Joachim
J
Physics Department T37, Technical University Munich, 85748 Garching, Germany. jdzubiel@ph.tum.de
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012492:Salts / Q000737:chemistry*
D010455:Peptides; D012492:Salts; D000409:Alanine