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
How 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
2016
High-Throughput Crystallography: Reliable and Efficient Identification of Fragment Hits
Schiebel J, Krimmer S, Röwer K, Knörlein A, Wang X, Park A, Stieler M, Ehrmann F, Fu K, Radeva N, Krug M, Huschmann F, Glöckner S, Weiss M, Mueller U, Klebe G, Heine A. High-Throughput Crystallography: Reliable and Efficient Identification of Fragment Hits. Structure 2016, 24: 1398-1409. PMID: 27452405, DOI: 10.1016/j.str.2016.06.010.Peer-Reviewed Original ResearchConceptsFragment-like moleculesFragment-based methodsSubsequent drug designHigh-quality diffraction dataFragment hitsHit identificationLead structuresDiverse fragmentsDrug designThroughput CrystallographyDiffraction dataStructural informationProtein crystalsCrystallographyElectron densityRefinement pipelineLigandsDrug developmentCompoundsMoleculesRefinement cycleStructureSuccessful applicationLow affinityHits