The transfer of an ion from water to a nonpolar medium with dielectric constant of ~3 (lipid bilayer) or 4 to 10 (interior of proteins) costs significant energy, as follows from the Born equation and from experiments. However, since the charged protein residues are ionizable, they simply lose their charges in the nonpolar environment, which costs relatively little at the neutral pH: ~4 to 7 kcal/mol for Asp, Glu, Lys, and Arg amino acid residues, according to the Henderson-Hasselbalch equation, ΔG = 2.3RT (pH - pK)''. The low energetic costs of such ionization effects have indeed been observed for protein mutants with buried ionizable residues.
The movement of an ion from water to a nonpolar medium with dielectric constant of ~3 (lipid bilayer) or 4 to 10 (interior of proteins) requires significant energy as per the Born equation and experimental findings. However, since charged protein residues are ionizable, they simply lose their charges in the nonpolar environment, which is energetically less costly at neutral pH: ~4 to 7 kcal/mol for Asp, Glu, Lys, and Arg amino acid residues, according to the Henderson-Hasselbalch equation, ΔG = 2.3RT (pH - pK).