Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor
Dawson TK, Dziedzic P, Robertson MJ, Cisneros J, Krimmer SG, Newton AS, Tirado-Rives J, Jorgensen WL. Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor. ACS Medicinal Chemistry Letters 2017, 8: 1287-1291. PMID: 29259749, PMCID: PMC5733268, DOI: 10.1021/acsmedchemlett.7b00384.Peer-Reviewed Original ResearchHydrogen bondsFEP resultsProtein-ligand hydrogen bondsExcellent aqueous solubilityLactam carbonyl groupDFT calculationsAqueous solubilityAmmonium groupsCarbonyl groupN distancesActive siteCrystal structureBondsQuinoline inhibitorsRelated quinolinesQuinolineNaphthyridinonesModel systemSolubilityCompoundsComplexesLys32CoordinationNMCalculationsHow Nothing Boosts Affinity: Hydrophobic Ligand Binding to the Virtually Vacated S1′ Pocket of Thermolysin
Krimmer S, Cramer J, Schiebel J, Heine A, Klebe G. How Nothing Boosts Affinity: Hydrophobic Ligand Binding to the Virtually Vacated S1′ Pocket of Thermolysin. Journal Of The American Chemical Society 2017, 139: 10419-10431. PMID: 28696673, DOI: 10.1021/jacs.7b05028.Peer-Reviewed Original ResearchConceptsWater moleculesPresent water moleculesWeak-binding ligandsAliphatic side chainsSpecificity pocketIsothermal titration calorimetrySolvent moleculesHigh-resolution crystallographyActive siteHydrophobic ligand bindingCrystalline stateElectron density mapsSide chainsTitration calorimetryS1 pocketNoble gas atomsSubstituentsThermodynamic signaturesFree energyHydration stateMoleculesLigands