title: Evaluation of Host-Guest Binding Thermodynamics of Model Cavities with Grid Cell Theory.
abstract: A previously developed cell theory model of liquid water was used to evaluate the excess thermodynamic properties of confined clusters of water molecules. The results are in good agreement with reference thermodynamic integration calculations, suggesting that the model is adequate to probe the thermodynamic properties of water at interfaces or in cavities. Next, the grid cell theory (GCT) method was applied to elucidate the thermodynamic signature of nonpolar association for a range of idealized host-guest systems. Polarity and geometry of the host cavities were systematically varied, and enthalpic and entropic solvent components were spatially resolved for detailed graphical analyses. Perturbations in the thermodynamic properties of water molecules upon guest binding are restricted to the immediate vicinity of the guest in solvent-exposed cavities, whereas longer-ranged perturbations are observed in buried cavities. Depending on the polarity and geometry of the host, water displacement by a nonpolar guest makes a small or large enthalpic or entropic contribution to the free energy of binding. Thus, no assumptions about the thermodynamic signature of the hydrophobic effect can be made in general. Overall the results warrant further applications of GCT to more complex systems such as protein-ligand complexes.
authors.affiliation: EaStCHEM School of Chemistry, Joseph Black Building , King's Buildings, Edinburgh EH9 3JJ, United Kingdom.
authors.forename: Julien
authors.initials: J
authors.lastname: Michel
authors.affiliation: Manchester Institute of Biotechnology, The University of Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.|School of Chemistry, The University of Manchester , Oxford Road, Manchester M13 9PL, United Kingdom.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Henchman
authors.affiliation: EaStCHEM School of Chemistry, Joseph Black Building , King's Buildings, Edinburgh EH9 3JJ, United Kingdom.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gerogiokas
authors.affiliation: Evotec (U.K.) Limited , Innovation Drive 114 Milton Park, Abingdon, Oxfordshire, OX14 4RZ, United Kingdom.
authors.forename: Michelle W Y
authors.initials: MW
authors.lastname: Southey
authors.affiliation: Evotec (U.K.) Limited , Innovation Drive 114 Milton Park, Abingdon, Oxfordshire, OX14 4RZ, United Kingdom.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mazanetz
authors.affiliation: Evotec (U.K.) Limited , Innovation Drive 114 Milton Park, Abingdon, Oxfordshire, OX14 4RZ, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Law