Barratt, Elizabeth, Bronowska, Agnieszka, Vondrášek, Jiří, Černý, Jiří, Bingham, Richard, Phillips, Simon and Homans, Steve W. (2006) Thermodynamic Penalty Arising from Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor. Journal of Molecular Biology, 362 (5). pp. 994-1003. ISSN 00222836Metadata only available from this repository.
Here, we examine the thermodynamic penalty arising from burial of a polar group in a hydrophobic pocket that forms part of the binding-site of the major urinary protein (MUP-I). X-ray crystal structures of the complexes of octanol, nonanol and 1,8 octan-diol indicate that these ligands bind with similar orientations in the binding pocket. Each complex is characterised by a bridging water molecule between the hydroxyl group of Tyr120 and the hydroxyl group of each ligand. The additional hydroxyl group of 1,8 octan-diol is thereby forced to reside in a hydrophobic pocket, and isothermal titration calorimetry experiments indicate that this is accompanied by a standard free energy penalty of + 21 kJ/mol with respect to octanol and + 18 kJ/mol with respect to nonanol. Consideration of the solvation thermodynamics of each ligand enables the “intrinsic” (solute–solute) interaction energy to be determined, which indicates a favourable enthalpic component and an entropic component that is small or zero. These data indicate that the thermodynamic penalty to binding derived from the unfavourable desolvation of 1,8 octan-diol is partially offset by a favourable intrinsic contribution. Quantum chemical calculations suggest that this latter contribution derives from favourable solute–solute dispersion interactions.
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Schools:||School of Applied Sciences|
|Depositing User:||Graham Stone|
|Date Deposited:||09 Oct 2009 08:55|
|Last Modified:||09 Oct 2009 08:55|
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