Side Chain Hydrophobicity Scale using the Tilted Beta-Barrel Protein PagP

Abstract

Membrane proteins fold via the transfer of amino acid side chains from aqueous solvent into a lipid bilayer. Thus, knowing the free energy change of side chain transfer from water to bilayer will contribute to understanding structure, function and energetics of membrane proteins. We have measured the transfer free energies for all twenty amino acids using the scaffold protein PagP in a DLPC bilayer. Compared to previously measured transfer free energies, the overall trend agrees: hydrophobic residues are favorable and hydrophilic residues are unfavorable in the bilayer. However, we have found that the transfer of some polar the side chains are more unfavorable than previously observed. We hypothesize that the physical basis for these new findings may be the tilt of PagP with respect to the membrane. These results indicate membrane protein stability is governed not only by side chain desolvation, but also structural features such as depth and angle in the membrane.