Peptides in Ionic Solutions: A Simulation Study of a Bis(penicillamine) Enkephalin in Sodium Acetate Solution

The bis (penicillamine) enkephalin, a small zwitterionic pentapeptide, has been studied in explicit 1.0 M sodium acetate solution with use of the molecular dynamics technique. During the simulation the association of multiple acetate ions with the positively charged N terminal region was observed. In addition, but to a far lesser extent, sodium ion binding to backbone carbonyl groups close to the negatively charged C terminus also occurred. Interesting individual events, such as the simultaneous binding of an acetate to a hydrogen of the N terminus and to backbone NH groups, were observed. Most often acetates only associated with the N terminal hydrogens. Subtle conformational changes in the peptide backbone were found as a consequence of acetate binding. These mechanistic observations are consistent with, and may be rationalized by, the known salting in and salting out properties of these ions and their relative positions in the Hofmeister (lyotropic) series.