title: Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory.
abstract: Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessible volume, but average water thermodynamic properties were not distinctive from other interfacial regions. Interfacial water molecules are frequently stabilized by enthalpy and destabilized entropy with respect to bulk, but counter-examples occasionally occur. Overall detailed inspection of the local coordinating environment appears necessary to gauge the thermodynamic stability of water in protein structures.
authors.affiliation: EaStCHEM School of Chemistry , Joseph Black Building, The King's Buildings, Edinburgh EH9 3JJ, United Kingdom.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gerogiokas
authors.affiliation: Evotec (U.K.) Limited , 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4SA, United Kingdom.
authors.forename: Michelle W Y
authors.initials: MW
authors.lastname: Southey
authors.affiliation: Evotec (U.K.) Limited , 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4SA, United Kingdom.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mazanetz
authors.affiliation: Evotec (U.K.) Limited , 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4SA, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Heifetz
authors.affiliation: Evotec (U.K.) Limited , 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4SA, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Bodkin
authors.affiliation: Evotec (U.K.) Limited , 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4SA, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Law
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, The King's Buildings, Edinburgh EH9 3JJ, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Michel
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001665:Binding Sites; D008024:Ligands; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D008024:Ligands; D011506:Proteins; D014867:Water