Stability of "salt bridges" in membrane proteins.

Proceedings of the National Academy of Sciences of the United States of America

PubMedID: 6591197

Honig BH, Hubbell WL. Stability of "salt bridges" in membrane proteins. Proc Natl Acad Sci USA. 1984;81(17):5412-6.
We estimate the free energies of transfer of ionized amino acid side chains in water to both their ion-paired and neutral hydrogen-bonded states in low-dielectric media. The difference between the two free energies corresponds to the proton transfer free energy in a "salt bridge" formed between acidic and basic groups (i.e., lysine and glutamic acid residues). Our approach is to use gas phase proton transfer data, pK values, and experimentally determined solvation energies to estimate the standard state free energy changes involved in transferring amino acid side chains, in both ionized and neutral form, from water (dielectric constant epsilon = 80) to vacuum (epsilon = 1). The familiar expressions for the charging energy of a sphere and dipole are used to interpolate between epsilon = 1 and epsilon = 80. Our results suggest that it costs approximately 10-16 kcal/mol to transfer a salt bridge from water to a medium of epsilon = 2-4, in ionized or neutral form within the resolution of our estimates. The proton transfer energy is thus approximately 0. The tendency of salt bridges to form additional hydrogen bonds in real proteins suggests that the ion pair will be present in most biological systems.