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Protein Sci. 2004 Oct;13(10):2600-12. Epub 2004 Aug 31.

Quantification of helix-helix binding affinities in micelles and lipid bilayers.

Author information

1
College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI 48109-1065, USA. almz@umich.edu

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.

PMID:
15340167
PMCID:
PMC2286553
DOI:
10.1110/ps.04850804
[Indexed for MEDLINE]
Free PMC Article

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