Electrostatic interactions across a beta-sheet.

The free energy consequences of electrostatic interactions across a model beta-sheet have been probed using a consensus zinc finger peptide. Relative folding free energies have been deduced from coupled peptide folding/metal binding reactions. The energies of the electrostatic interactions have been isolated via double mutant cycles performed at a series of NaCl concentrations. The observed favorable free energies associated with potential ion pairs are modest, less than 0.5 kcal/mol. Unfavorable interactions due to like-charge pairs of similar magnitude were also observed. The largest effects, both favorable and unfavorable, involved interactions with aspartic acid. These observations are consistent with electrostatic interactions occurring without contact ion pair formation with the larger interaction energies involving aspartic acid being due to the relative lack of flexibility of its side chain.