Nuclear Physics/Molecules - an Analogy< Nuclear Physics
A theoretical approach for estimating association free energies of -helices in nonpolar media has been developed. The parameters of energy functions have been derived from G values of mutants in water-soluble teins and partitioning of organic solutes between water and nonpolar solvents. The proposed approach was verified successfully against three sets of published data: (1) dissociation constants of -helical oligomers formed by 27 hydrophobic peptides; (2) stabilities of 22 bacteriorhodopsin mutants, and (3) protein-ligand binding affinities in aqueous solution. It has been found that coalescence of helices is driven exclusively by van der Waals interactions and H-bonds, whereas the principal destabilizing contributions are represented by side-chain conformational entropy and transfer energy of atoms from a detergent or lipid to the protein interior. Electrostatic interactions of -helices were relatively weak but important for reproducing the experimental data. Immobilization free energy, which originates from restricting rotational and translational rigid-body movements of molecules during their association, was found to be less than 1 kcal/mole. The energetics of amino acid substitutions in bacteriorhodopsin was complicated by specific binding of lipid and water molecules to cavities created in certain mutants.
Keywords: binding; thermodynamics; potentials; solvation; membranes; micelles; -helix; entropy; peptides; bacteriorhodopsin; glycophorin A
Abbreviations: vdW, van der Waals interactions • ASA, accessible surface area • PDB, Protein Data Bank • SDS, sodium dodecylsulfate • DPC, N-dodecylphosphocholine • DDMAB, N-dodecyl-N,N-(dimethylammonio) butyrate • DMPC, 1,2 Dimytristoyl-sn-glycerol-3-phosphocholine • GpA, glycophorin A • MS1, QLLIAVLLLIAVNLILLIAVARLRYLVG • L7NL11, RARL7NL11GILIN • L19, RARL19GILIN • L16, KKGL7WL9KKA • Y16, KKGL7YL9KKA • L22, KKGL10WL12KKA • Y22, KKGL10YL12KK.
Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.04850804.