title: Quantification of helix-helix binding affinities in micelles and lipid bilayers.
abstract: A theoretical approach for estimating association free energies of alpha-helices in nonpolar media has been developed. The parameters of energy functions have been derived from DeltaDeltaG values of mutants in water-soluble proteins 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 alpha-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 alpha-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.
authors.affiliation: College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI 48109-1065, USA. almz@umich.edu
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Lomize
authors.forename: I D
authors.initials: ID
authors.lastname: Pogozheva
authors.forename: H I
authors.initials: HI
authors.lastname: Mosberg
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001436:Bacteriorhodopsins / Q000737:chemistry / Q000235:genetics; D019281:Dimerization; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008823:Micelles; D008956:Models, Chemical; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D008024:Ligands; D008051:Lipid Bilayers; D008565:Membrane Proteins; D008823:Micelles; D010455:Peptides; D012996:Solutions; D014867:Water; D001436:Bacteriorhodopsins