Electrostatic screening of charge and dipole interactions with the helix backbone.

Electrostatic interactions in proteins are potentially quite strong, but these interactions are mitigated by the screening effects of water, ions, and nearby protein atoms. The early work of Kirkwood and Westheimer on small organic molecules showed that the extent of the screening may depend on whether charged or dipolar groups are involved. The dielectric and ionic screening of the interactions between the dipolar backbone amide groups of monomeric alpha helices and either (i) solvent-exposed charges or (ii) solvent-exposed dipoles at the amino terminus was measured. The dielectric screening effects are an order of magnitude greater for the backbone-charge interactions than for the backbone-dipole interactions, and the ionic strength dependence is substantially different in the two cases. These results suggest that interactions that involve the dipolar groups of proteins may be relatively more important for stability and function than is generally thought.