Strong solute-solute dispersive interactions in a protein-ligand complex

J Am Chem Soc. 2005 Dec 7;127(48):17061-7. doi: 10.1021/ja055454g.


The contributions of solute-solute dispersion interactions to binding thermodynamics have generally been thought to be small, due to the surmised equality between solute-solvent dispersion interactions prior to the interaction versus solute-solute dispersion interactions following the interaction. The thermodynamics of binding of primary alcohols to the major urinary protein (MUP-I) indicate that this general assumption is not justified. The enthalpy of binding becomes more favorable with increasing chain length, whereas the entropy of binding becomes less favorable, both parameters showing a linear dependence. Despite the hydrophobicity of the interacting species, these data show that binding is not dominated by the classical hydrophobic effect, but can be attributed to favorable ligand-protein dispersion interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry*
  • Alcohols / metabolism*
  • Animals
  • Binding Sites
  • Calorimetry
  • Crystallography, X-Ray
  • Ligands
  • Mice
  • Models, Molecular
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Thermodynamics
  • Water / chemistry
  • Water / metabolism


  • Alcohols
  • Ligands
  • Proteins
  • major urinary proteins
  • Water