Quantifying the Entropy of Binding for Water Molecules In Protein Cavities by Computing Correlations

Add to your list(s) Download to your calendar using vCal

• David Huggins, University of Cambridge
• Friday 27 February 2015, 13:00-14:00
• Todd Hamied Room, Dept. of Chemistry.

If you have a question about this talk, please contact Lucy Colwell.

Protein structural analysis demonstrates that water molecules are commonly found in the internal cavities of proteins. Analysis of experimental data on the entropies of inorganic crystals suggests that the entropic cost of transferring such a water molecule to a protein cavity will not typically be greater than 7.0 cal/mol/K per water molecule, corresponding to a contribution of approximately +2.0 kcal/mol to the free energy. In this study, we employ the statistical mechanical method of inhomogeneous fluid solvation theory to quantify the enthalpic and entropic contributions of individual water molecules in nineteen protein cavities across five different proteins. We utilize information theory to develop a rigorous estimate of the total two-particle entropy, yielding a complete framework to calculate hydration free energies. We show that predictions from inhomogeneous fluid solvation theory are in excellent agreement with predictions from free-energy perturbation and that these predictions are consistent with experimental estimates. However, the results suggest that water molecules in protein cavities containing charged residues may be subject to entropy changes that contribute more than +2.0 kcal/mol to the free energy. In all cases, these unfavourable entropy changes are predicted to be dominated by highly-favourable enthalpy changes. These findings are relevant to the study of bridging water molecules at protein-protein interfaces as well as in complexes with cognate ligands and small-molecule inhibitors.

This talk is part of the Extra Theoretical Chemistry Seminars series.

This talk is included in these lists:

• All Talks (aka the CURE list)
• Department of Chemistry
• Featured lists
• Lennard-Jones Centre external
• School of Physical Sciences
• Todd Hamied Room, Dept. of Chemistry

Note that ex-directory lists are not shown.