Molecular mechanisms of ion-specific effects on proteins

J Am Chem Soc. 2012 Jun 20;134(24):10039-46. doi: 10.1021/ja301297g. Epub 2012 Jun 11.

Abstract

The specific binding sites of Hofmeister ions with an uncharged 600-residue elastin-like polypeptide, (VPGVG)(120), were elucidated using a combination of NMR and thermodynamic measurements along with molecular dynamics simulations. It was found that the large soft anions such as SCN(-) and I(-) interact with the polypeptide backbone via a hybrid binding site that consists of the amide nitrogen and the adjacent α-carbon. The hydrocarbon groups at these sites bear a slight positive charge, which enhances anion binding without disrupting specific hydrogen bonds to water molecules. The hydrophobic side chains do not contribute significantly to anion binding or the corresponding salting-in behavior of the biopolymer. Cl(-) binds far more weakly to the amide nitrogen/α-carbon binding site, while SO(4)(2-) is repelled from both the backbone and hydrophobic side chains of the polypeptide. The Na(+) counterions are also repelled from the polypeptide. The identification of these molecular-level binding sites provides new insights into the mechanism of peptide-anion interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anions / chemistry
  • Binding Sites
  • Hydrogen Bonding
  • Ions / chemistry*
  • Molecular Dynamics Simulation
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry*
  • Thermodynamics

Substances

  • Anions
  • Ions
  • Peptides
  • elastin polypentapeptide