2021
Indoloxytriazines as binding molecules for the JAK2 JH2 pseudokinase domain and its V617F variant
Newton AS, Liosi ME, Henry SP, Deiana L, Faver JC, Krimmer SG, Puleo DE, Schlessinger J, Jorgensen WL. Indoloxytriazines as binding molecules for the JAK2 JH2 pseudokinase domain and its V617F variant. Tetrahedron Letters 2021, 77: 153248. PMID: 34393283, PMCID: PMC8357305, DOI: 10.1016/j.tetlet.2021.153248.Peer-Reviewed Original Research
2017
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 systemSolubilityCompoundsComplexesLys32CoordinationNMCalculations
2016
Impact of Surface Water Layers on Protein–Ligand Binding: How Well Are Experimental Data Reproduced by Molecular Dynamics Simulations in a Thermolysin Test Case?
Betz M, Wulsdorf T, Krimmer S, Klebe G. Impact of Surface Water Layers on Protein–Ligand Binding: How Well Are Experimental Data Reproduced by Molecular Dynamics Simulations in a Thermolysin Test Case? Journal Of Chemical Information And Modeling 2016, 56: 223-233. PMID: 26691064, DOI: 10.1021/acs.jcim.5b00621.Peer-Reviewed Original ResearchConceptsObserved structure-activity relationshipsLocal water structureProtein-ligand bindingMolecular dynamics simulationsStructure-activity relationshipsHigh-resolution crystal structuresSolvation sitesWater structureSurface water networkWater rearrangementCrystal structureDesolvation effectsDifference electronMolecular dynamicsDynamics simulationsLigand portionWater networkDrug bindingContribution of waterWater layerComplexesSurface water layerWaterPhosphonamidatesStructure