2018
Bayesian analysis of isothermal titration calorimetry for binding thermodynamics
Nguyen T, Rustenburg A, Krimmer S, Zhang H, Clark J, Novick P, Branson K, Pande V, Chodera J, Minh D. Bayesian analysis of isothermal titration calorimetry for binding thermodynamics. PLOS ONE 2018, 13: e0203224. PMID: 30212471, PMCID: PMC6136728, DOI: 10.1371/journal.pone.0203224.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
Active Site Mapping of an Aspartic Protease by Multiple Fragment Crystal Structures: Versatile Warheads To Address a Catalytic Dyad
Radeva N, Schiebel J, Wang X, Krimmer S, Fu K, Stieler M, Ehrmann F, Metz A, Rickmeyer T, Betz M, Winquist J, Park A, Huschmann F, Weiss M, Mueller U, Heine A, Klebe G. Active Site Mapping of an Aspartic Protease by Multiple Fragment Crystal Structures: Versatile Warheads To Address a Catalytic Dyad. Journal Of Medicinal Chemistry 2016, 59: 9743-9759. PMID: 27726357, DOI: 10.1021/acs.jmedchem.6b01195.Peer-Reviewed Original ResearchConceptsFunctional groupsAspartic protease endothiapepsinCatalytic dyadCarboxylic acid fragmentOxygen functional groupsNovel functional groupsActive site mappingSteric demandWater moleculesFragment-growing strategyCrystal structureSide chainsFragment libraryHigh-quality crystalsS1 pocketScreening cascadeAcid fragmentCrystallographySpecificity pocketRelated fragmentsWarheadSix Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study
Schiebel J, Radeva N, Krimmer S, Wang X, Stieler M, Ehrmann F, Fu K, Metz A, Huschmann F, Weiss M, Mueller U, Heine A, Klebe G. Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study. ACS Chemical Biology 2016, 11: 1693-1701. PMID: 27028906, DOI: 10.1021/acschembio.5b01034.Peer-Reviewed Original Research
2015
Thermodynamics of protein–ligand interactions as a reference for computational analysis: how to assess accuracy, reliability and relevance of experimental data
Krimmer S, Klebe G. Thermodynamics of protein–ligand interactions as a reference for computational analysis: how to assess accuracy, reliability and relevance of experimental data. Journal Of Computer-Aided Molecular Design 2015, 29: 867-883. PMID: 26376645, DOI: 10.1007/s10822-015-9867-y.Peer-Reviewed Original Research