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SUMMARY:Quantifying the Entropy of Binding for Water Molecules In Protein 
 Cavities by Computing Correlations - David Huggins\, University of Cambrid
 ge
DTSTART:20150227T130000Z
DTEND:20150227T140000Z
UID:TALK57238@talks.cam.ac.uk
CONTACT:Lucy Colwell
DESCRIPTION:Protein structural analysis demonstrates that water molecules 
 are\ncommonly found in the internal cavities of proteins. Analysis of\nexp
 erimental data on the entropies of inorganic crystals suggests that\nthe e
 ntropic cost of transferring such a water molecule to a protein\ncavity wi
 ll not typically be greater than 7.0 cal/mol/K per water\nmolecule\, corre
 sponding to a contribution of approximately +2.0\nkcal/mol to the free ene
 rgy. In this study\, we employ the statistical\nmechanical method of inhom
 ogeneous fluid solvation theory to quantify\nthe enthalpic and entropic co
 ntributions of individual water molecules\nin nineteen protein cavities ac
 ross five different proteins. We\nutilize information theory to develop a 
 rigorous estimate of the total\ntwo-particle entropy\, yielding a complete
  framework to calculate\nhydration free energies. We show that predictions
  from inhomogeneous\nfluid solvation theory are in excellent agreement wit
 h predictions\nfrom free-energy perturbation and that these predictions ar
 e\nconsistent with experimental estimates. However\, the results suggest\n
 that water molecules in protein cavities containing charged residues\nmay 
 be subject to entropy changes that contribute more than +2.0\nkcal/mol to 
 the free energy. In all cases\, these unfavourable entropy\nchanges are pr
 edicted to be dominated by highly-favourable enthalpy\nchanges. These find
 ings are relevant to the study of bridging water\nmolecules at protein-pro
 tein interfaces as well as in complexes with\ncognate ligands and small-mo
 lecule inhibitors.
LOCATION:Todd Hamied Room\, Dept. of Chemistry
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