The recent perspectives on membrane protein insertion, protein–bilayer interactions, and amino acid side hydrophobicity (J. Gen. Physiol., 129:351–377) provide an excellent opportunity to return to the fundamental issue of the solvation of amino acids and their thermodynamic stability in different environments (Andersen, 2007). Though seemingly “solved” long ago, in recent years this issue has resurfaced in discussions of the voltage-gating mechanism of K+ channels, and the likely configuration of charged arginine side chain of the voltage sensor with respect to the membrane lipids (Mackinnon, 2005). The issues have, at some level, been wrapped in controversy. The perspectives point to ways to dissipate some of the controversies, upon which I wish to elaborate further in this letter.
First, let us recall the obvious. Water is a good “high dielectric” solvent for polar and charged species and a...
