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 affinityHitsImpact 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