Gerhard Klebe

Drug Design Group, Philipps-Universität Marburg

Affiliated withPhilipps-Universität Marburg

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JoVE Journal Publications

ArticleTotal : 1	Year
Publication title Cited by 18	2021

Other Publications

Article	Year
Price for Opening the Transient Specificity Pocket in Human Aldose Reductase upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis. ACS chemical biology\| PubMed ID: 28287700	2017
pH-dependent binding modes observed in trypsin crystals: lessons for structure-based drug design. Chembiochem : a European journal of chemical biology\| PubMed ID: 11921406	2002
Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors. Angewandte Chemie (International ed. in English)\| PubMed ID: 12203463	2002
DrugScore meets CoMFA: adaptation of fields for molecular comparison (AFMoC) or how to tailor knowledge-based pair-potentials to a particular protein. Journal of medicinal chemistry\| PubMed ID: 12213058	2002
Trypsin mutants for structure-based drug design: expression, refolding and crystallisation. Biological chemistry\| PubMed ID: 12437122	2002
Reconstructing the binding site of factor Xa in trypsin reveals ligand-induced structural plasticity. Journal of molecular biology\| PubMed ID: 12527302	2003
Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis. Journal of medicinal chemistry\| PubMed ID: 12646024	2003
Crystal structure of 2-methylisocitrate lyase (PrpB) from Escherichia coli and modelling of its ligand bound active centre. Journal of molecular biology\| PubMed ID: 12706720	2003
ZZ made EZ: influence of inhibitor configuration on enzyme selectivity. Journal of molecular biology\| PubMed ID: 12850145	2003
Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug... Chembiochem : a European journal of chemical biology\| PubMed ID: 14523925	2003
Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening. Journal of molecular biology\| PubMed ID: 15050823	2004
Non-thiol farnesyltransferase inhibitors: N-(4-tolylacetylamino-3-benzoylphenyl)-3-arylfurylacrylic acid amides. Bioorganic & medicinal chemistry\| PubMed ID: 15358286	2004
Non-thiol farnesyltransferase inhibitors: utilization of the far aryl binding site by 5-cinnamoylaminobenzophenones. Archiv der Pharmazie\| PubMed ID: 15362122	2004
Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model. Journal of medicinal chemistry\| PubMed ID: 15481976	2004
An old target revisited: two new privileged skeletons and an unexpected binding mode for HIV-protease inhibitors. Angewandte Chemie (International ed. in English)\| PubMed ID: 15822136	2005
Mechanism and substrate specificity of tRNA-guanine transglycosylases (TGTs): tRNA-modifying enzymes from the three different kingdoms of life share a common catalytic mechanism. Chembiochem : a European journal of chemical biology\| PubMed ID: 16206323	2005
Hydroxyethylene sulfones as a new scaffold to address aspartic proteases: design, synthesis, and structural characterization. Journal of medicinal chemistry\| PubMed ID: 16220977	2005
A simple protocol to estimate differences in protein binding affinity for enantiomers without prior resolution of racemates. Angewandte Chemie (International ed. in English)\| PubMed ID: 16374786	2006
An efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS coronavirus main protease (SARS-CoV Mpro) inhibitors. Chembiochem : a European journal of chemical biology\| PubMed ID: 16688706	2006
Unexpected novel binding mode of pyrrolidine-based aspartyl protease inhibitors: design, synthesis and crystal structure in complex with HIV protease. ChemMedChem\| PubMed ID: 16892342	2006
Integrated approach using protein and ligand information to analyze selectivity- and affinity-determining features of carbonic anhydrase isozymes. ChemMedChem\| PubMed ID: 16902938	2006
Development, validation, and application of adapted PEOE charges to estimate pKa values of functional groups in protein-ligand complexes. Proteins\| PubMed ID: 16927370	2006
Crystal structure of Bacillus subtilis S-adenosylmethionine:tRNA ribosyltransferase-isomerase. Biochemical and biophysical research communications\| PubMed ID: 17083917	2006
Atypical protonation states in the active site of HIV-1 protease: a computational study. Journal of chemical information and modeling\| PubMed ID: 17503762	2007
Crystal structures of tRNA-guanine transglycosylase (TGT) in complex with novel and potent inhibitors unravel pronounced induced-fit adaptations and suggest dimer formation upon substrate bi... Journal of molecular biology\| PubMed ID: 17524419	2007
Use of biotin derivatives to probe conformational changes in proteins. The Journal of biological chemistry\| PubMed ID: 17545162	2007
Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste. Angewandte Chemie (International ed. in English)\| PubMed ID: 17705204	2007
Novel deoxyxylulosephosphate-reductoisomerase inhibitors: fosmidomycin derivatives with spacious acyl residues. Archiv der Pharmazie\| PubMed ID: 17806130	2007
Thermodynamic inhibition profile of a cyclopentyl and a cyclohexyl derivative towards thrombin: the same but for different reasons. Angewandte Chemie (International ed. in English)\| PubMed ID: 17902081	2007
Glutamate versus glutamine exchange swaps substrate selectivity in tRNA-guanine transglycosylase: insight into the regulation of substrate selectivity by kinetic and crystallographic studies... Journal of molecular biology\| PubMed ID: 17949745	2007
KNOBLE: a knowledge-based approach for the design and synthesis of readily accessible small-molecule chemical probes to test protein binding. Angewandte Chemie (International ed. in English)\| PubMed ID: 17955562	2007
Use of 3D QSAR models for database screening: a feasibility study. Journal of chemical information and modeling\| PubMed ID: 18211050	2008
Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold. Journal of medicinal chemistry\| PubMed ID: 18348517	2008
SFCscore: scoring functions for affinity prediction of protein-ligand complexes. Proteins\| PubMed ID: 18442132	2008
Studies addressing the importance of charge in the binding of fosmidomycin-like molecules to deoxyxylulosephosphate reductoisomerase. ChemMedChem\| PubMed ID: 18470849	2008
Development of benzophenone-based farnesyltransferase inhibitors as novel antimalarials. ChemMedChem\| PubMed ID: 18470859	2008
Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. Journal of molecular biology\| PubMed ID: 18692068	2008
Turns revisited: a uniform and comprehensive classification of normal, open, and reverse turn families minimizing unassigned random chain portions. Proteins\| PubMed ID: 18704930	2009
Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based inhibitors. ChemMedChem\| PubMed ID: 18720485	2008
Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors. ChemMedChem\| PubMed ID: 18752222	2008
Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors. Bioorganic & medicinal chemistry\| PubMed ID: 18760609	2008
Crystal structure analysis and in silico pKa calculations suggest strong pKa shifts of ligands as driving force for high-affinity binding to TGT. Chembiochem : a European journal of chemical biology\| PubMed ID: 19199329	2009
Evolutionary construction of multiple graph alignments for the structural analysis of biomolecules. Bioinformatics (Oxford, England)\| PubMed ID: 19286830	2009
Structure-based optimization of aldose reductase inhibitors originating from virtual screening. ChemMedChem\| PubMed ID: 19301313	2009
An integrative approach combining noncovalent mass spectrometry, enzyme kinetics and X-ray crystallography to decipher Tgt protein-protein and protein-RNA interaction. Journal of molecular biology\| PubMed ID: 19627989	2009
Secbase: database module to retrieve secondary structure elements with ligand binding motifs. Journal of chemical information and modeling\| PubMed ID: 19807134	2009
How to replace the residual solvation shell of polar active site residues to achieve nanomolar inhibition of tRNA-guanine transglycosylase. ChemMedChem\| PubMed ID: 19894214	2009
Pyrrolidine derivatives as plasmepsin inhibitors: binding mode analysis assisted by molecular dynamics simulations of a highly flexible protein. ChemMedChem\| PubMed ID: 20112327	2010
Fragment-based lead discovery: screening and optimizing fragments for thermolysin inhibition. ChemMedChem\| PubMed ID: 20394106	2010
Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plant Coleus blumei Benth. Acta crystallographica. Section D, Biological crystallography\| PubMed ID: 20445235	2010
Bidentate Zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry. ChemMedChem\| PubMed ID: 20629007	2010
GARLig: a fully automated tool for subset selection of large fragment spaces via a self-adaptive genetic algorithm. Journal of chemical information and modeling\| PubMed ID: 20795677	2010
fconv: Format conversion, manipulation and feature computation of molecular data. Bioinformatics (Oxford, England)\| PubMed ID: 21335612	2011
SEGA: semiglobal graph alignment for structure-based protein comparison. IEEE/ACM transactions on computational biology and bioinformatics\| PubMed ID: 21339532	2011
Superposition and alignment of labeled point clouds. IEEE/ACM transactions on computational biology and bioinformatics\| PubMed ID: 21358005	2011
Stereo- and regioselective azide/alkyne cycloadditions in carbonic anhydrase II via tethering, monitored by crystallography and mass spectrometry. Chemistry (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 21506176	2011
MiniMuDS: a new optimizer using knowledge-based potentials improves scoring of docking solutions. Journal of chemical information and modeling\| PubMed ID: 21528908	2011
[M2 inhibitors and neuraminidase inhibitors]. Pharmazie in unserer Zeit\| PubMed ID: 21630541	2011
Two solutions for the same problem: multiple binding modes of pyrrolidine-based HIV-1 protease inhibitors. Journal of molecular biology\| PubMed ID: 21762812	2011
DSX: a knowledge-based scoring function for the assessment of protein-ligand complexes. Journal of chemical information and modeling\| PubMed ID: 21863864	2011
Development of improved PPARβ/δ inhibitors. ChemMedChem\| PubMed ID: 22025402	2012
Cofactor-binding sites in proteins of deviating sequence: comparative analysis and clustering in torsion angle, cavity, and fold space. Proteins\| PubMed ID: 22095739	2012
Concise and efficient syntheses of preQ1 base, Q base, and (ent)-Q base. Organic & biomolecular chemistry\| PubMed ID: 23032613	2012
Targeting the blind spot of polycationic nanocarrier-based siRNA delivery. ACS nano\| PubMed ID: 23036046	2012
Novel type II fatty acid biosynthesis (FAS II) inhibitors as multistage antimalarial agents. ChemMedChem\| PubMed ID: 23341167	2013
Launching spiking ligands into a protein-protein interface: a promising strategy to destabilize and break interface formation in a tRNA modifying enzyme. ACS chemical biology\| PubMed ID: 23534552	2013
Investigation of specificity determinants in bacterial tRNA-guanine transglycosylase reveals queuine, the substrate of its eucaryotic counterpart, as inhibitor. PloS one\| PubMed ID: 23704982	2013
Cavities tell more than sequences: exploring functional relationships of proteases via binding pockets. Journal of chemical information and modeling\| PubMed ID: 23834203	2013
Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics. Biochimica et biophysica acta\| PubMed ID: 24792574	2014
Chasing protons: how isothermal titration calorimetry, mutagenesis, and pKa calculations trace the locus of charge in ligand binding to a tRNA-binding enzyme. Journal of medicinal chemistry\| PubMed ID: 24955548	2014
Beyond affinity: enthalpy-entropy factorization unravels complexity of a flat structure-activity relationship for inhibition of a tRNA-modifying enzyme. Journal of medicinal chemistry\| PubMed ID: 24960372	2014
Hot-spot analysis to dissect the functional protein-protein interface of a tRNA-modifying enzyme. Proteins\| PubMed ID: 24975703	2014
Large-scale mining for similar protein binding pockets: with RAPMAD retrieval on the fly becomes real. Journal of chemical information and modeling\| PubMed ID: 25474400	2015
Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors. Angewandte Chemie (International ed. in English)\| PubMed ID: 25630461	2015
What Glues a Homodimer Together: Systematic Analysis of the Stabilizing Effect of an Aromatic Hot Spot in the Protein-Protein Interface of the tRNA-Modifying Enzyme Tgt. ACS chemical biology\| PubMed ID: 25951081	2015
Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin. International journal of molecular sciences\| PubMed ID: 26287174	2015
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\| PubMed ID: 26376645	2015
An Immucillin-Based Transition-State-Analogous Inhibitor of tRNA-Guanine Transglycosylase (TGT). Chemistry (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 26991861	2016
Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study. ACS chemical biology\| PubMed ID: 27028906	2016
Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library. Acta crystallographica. Section F, Structural biology communications\| PubMed ID: 27139825	2016
Fingerprint Kernels for Protein Structure Comparison. Molecular informatics\| PubMed ID: 27477463	2012
Occupying a flat subpocket in a tRNA-modifying enzyme with ordered or disordered side chains: Favorable or unfavorable for binding? Bioorganic & medicinal chemistry\| PubMed ID: 27501913	2016
A False-Positive Screening Hit in Fragment-Based Lead Discovery: Watch out for the Red Herring. Angewandte Chemie (International ed. in English)\| PubMed ID: 28097765	2017
Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin. Angewandte Chemie (International ed. in English)\| PubMed ID: 28371253	2017
Soaking suggests "alternative facts": Only co-crystallization discloses major ligand-induced interface rearrangements of a homodimeric tRNA-binding protein indicating a novel mode-of-inhibit... PloS one\| PubMed ID: 28419165	2017
From Structure to Function: A New Approach to Detect Functional Similarity among Proteins Independent from Sequence and Fold Homology. Angewandte Chemie (International ed. in English)\| PubMed ID: 29712060	2001
Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase. Biochemistry\| PubMed ID: 29862811	2018
Paradoxically, Most Flexible Ligand Binds Most Entropy-Favored: Intriguing Impact of Ligand Flexibility and Solvation on Drug-Kinase Binding. Journal of medicinal chemistry\| PubMed ID: 29909615	2018
Swapping Interface Contacts in the Homodimeric tRNA-Guanine Transglycosylase: An Option for Functional Regulation. Angewandte Chemie (International ed. in English)\| PubMed ID: 29927035	2018
Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase. Chemistry (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 29939431	2018
On the Implication of Water on Fragment-to-Ligand Growth in Kinase Binding Thermodynamics. ChemMedChem\| PubMed ID: 30058283	2018
Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes. Nature communications\| PubMed ID: 30177695	2018
Strategies for Late-Stage Optimization: Profiling Thermodynamics by Preorganization and Salt Bridge Shielding. Journal of medicinal chemistry\| PubMed ID: 31633354	2019
Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction. ACS chemical biology\| PubMed ID: 31638770	2019
Protein-Ligand Complex Solvation Thermodynamics: Development, Parameterization, and Testing of GIST-Based Solvent Functionals. Journal of chemical information and modeling\| PubMed ID: 31922753	2020
Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors. ACS chemical biology\| PubMed ID: 32027480	2020
Role of Water Molecules in Protein-Ligand Dissociation and Selectivity Discrimination: Analysis of the Mechanisms and Kinetics of Biomolecular Solvation Using Molecular Dynamics. Journal of chemical information and modeling\| PubMed ID: 32078307	2020
The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II. Biomolecules\| PubMed ID: 32230853	2020
A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II. Biomolecules\| PubMed ID: 32235320	2020
F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening. Structure (London, England : 1993)\| PubMed ID: 32413289	2020
Fragment-Based Discovery of Non-bisphosphonate Binders of Trypanosoma brucei Farnesyl Pyrophosphate Synthase. Chembiochem : a European journal of chemical biology\| PubMed ID: 32537808	2020
Fragment Binding to Kinase Hinge: If Charge Distribution and Local pK Shifts Mislead Popular Bioisosterism Concepts. Angewandte Chemie (International ed. in English)\| PubMed ID: 33021032	2021
Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses. ChemMedChem\| PubMed ID: 33029876	2021
The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase. ACS chemical biology\| PubMed ID: 33166460	2020
Advancing GIST-Based Solvent Functionals through Multiobjective Optimization of Solvent Enthalpy and Entropy Scoring Terms. Journal of chemical information and modeling\| PubMed ID: 33264016	2020
How a Fragment Draws Attention to Selectivity Discriminating Features between the Related Proteases Trypsin and Thrombin. Journal of medicinal chemistry\| PubMed ID: 33471524	2021