2016
Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands
Krimmer S, Cramer J, Betz M, Fridh V, Karlsson R, Heine A, Klebe G. Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands. Journal Of Medicinal Chemistry 2016, 59: 10530-10548. PMID: 27933956, DOI: 10.1021/acs.jmedchem.6b00998.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesDose-Response Relationship, DrugKineticsLigandsMolecular Dynamics SimulationMolecular StructureProteinsStructure-Activity RelationshipSurface PropertiesThermodynamicsWaterConceptsDifferent hydrophobic substituentsKinetic binding profilesProtein-bound ligandsParent ligandSurface plasmon resonanceWater moleculesProtein-bound inhibitorThermolysin inhibitorsHigh-resolution crystallographyCongeneric seriesRational designWater networkMD simulationsHydrophobic substituentsPlasmon resonanceSubstituentsAffinity enhancementLigandsWater polygonsWater layerSurface water networkSurface water layerBinding signatureResidence timeCrystallography
2014
Methyl, Ethyl, Propyl, Butyl: Futile But Not for Water, as the Correlation of Structure and Thermodynamic Signature Shows in a Congeneric Series of Thermolysin Inhibitors
Krimmer S, Betz M, Heine A, Klebe G. Methyl, Ethyl, Propyl, Butyl: Futile But Not for Water, as the Correlation of Structure and Thermodynamic Signature Shows in a Congeneric Series of Thermolysin Inhibitors. ChemMedChem 2014, 9: 833-846. PMID: 24623396, DOI: 10.1002/cmdc.201400013.Peer-Reviewed Original ResearchMeSH KeywordsDose-Response Relationship, DrugEnzyme InhibitorsModels, MolecularMolecular StructureOrganophosphonatesStructure-Activity RelationshipThermodynamicsThermolysinWaterConceptsWater moleculesFirst solvation layerThermodynamic binding profilesProtein-ligand binding processHigh-resolution crystal structuresIsothermal titration calorimetrySolvation patternsCorrelation of structureSolvation layerEntropy-driven bindingThermolysin inhibitorsCongeneric seriesSingle methyl groupCrystal structureWater arrangementSolvent-exposed surfaceTitration calorimetryBinding processMethyl groupS2 pocketSubstituentsComplex formationBinding propertiesLigand binding propertiesBiological systems