Gerhard Klebe Drug Design Group, Institute of Pharmaceutical Chemistry Philipps-Universität Marburg Biography Publications Institution JoVE Articles Gerhard Klebe has not added a biography. If you are Gerhard Klebe and would like to personalize this page please email our Author Liaison for assistance. Publications How a Fragment Draws Attention to Selectivity Discriminating Features Between the Related Proteases Trypsin and Thrombin Journal of Medicinal Chemistry. Feb, 2021 | Pubmed ID: 33471524 Two Methods, One Goal: Structural Differences Between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses ChemMedChem. Jan, 2021 | Pubmed ID: 33029876 Fragment Binding to Kinase Hinge: If Charge Distribution and Local PK Shifts Mislead Popular Bioisosterism Concepts Angewandte Chemie (International Ed. in English). 01, 2021 | Pubmed ID: 33021032 Advancing GIST-Based Solvent Functionals Through Multiobjective Optimization of Solvent Enthalpy and Entropy Scoring Terms Journal of Chemical Information and Modeling. Dec, 2020 | Pubmed ID: 33264016 The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric TRNA-Guanine Transglycosylase ACS Chemical Biology. 11, 2020 | Pubmed ID: 33166460 Fragment-Based Discovery of Non-bisphosphonate Binders of Trypanosoma Brucei Farnesyl Pyrophosphate Synthase Chembiochem : a European Journal of Chemical Biology. Nov, 2020 | Pubmed ID: 32537808 F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening Structure (London, England : 1993). 06, 2020 | Pubmed ID: 32413289 A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library Against Human Carbonic Anhydrase II Biomolecules. 03, 2020 | Pubmed ID: 32235320 The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II Biomolecules. 03, 2020 | Pubmed ID: 32230853 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. 03, 2020 | Pubmed ID: 32078307 Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors ACS Chemical Biology. 03, 2020 | Pubmed ID: 32027480 Protein-Ligand Complex Solvation Thermodynamics: Development, Parameterization, and Testing of GIST-Based Solvent Functionals Journal of Chemical Information and Modeling. 03, 2020 | Pubmed ID: 31922753 Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction ACS Chemical Biology. 12, 2019 | Pubmed ID: 31638770 Strategies for Late-Stage Optimization: Profiling Thermodynamics by Preorganization and Salt Bridge Shielding Journal of Medicinal Chemistry. 11, 2019 | Pubmed ID: 31633354 Intriguing Role of Water in Protein-ligand Binding Studied by Neutron Crystallography on Trypsin Complexes Nature Communications. 09, 2018 | Pubmed ID: 30177695 On the Implication of Water on Fragment-to-Ligand Growth in Kinase Binding Thermodynamics ChemMedChem. 09, 2018 | Pubmed ID: 30058283 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). Jul, 2018 | Pubmed ID: 29939431 Swapping Interface Contacts in the Homodimeric TRNA-Guanine Transglycosylase: An Option for Functional Regulation Angewandte Chemie (International Ed. in English). 08, 2018 | Pubmed ID: 29927035 Paradoxically, Most Flexible Ligand Binds Most Entropy-Favored: Intriguing Impact of Ligand Flexibility and Solvation on Drug-Kinase Binding Journal of Medicinal Chemistry. Jul, 2018 | Pubmed ID: 29909615 Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic TRNA-Guanine Transglycosylase Biochemistry. 07, 2018 | Pubmed ID: 29862811 Soaking Suggests "alternative Facts": Only Co-crystallization Discloses Major Ligand-induced Interface Rearrangements of a Homodimeric TRNA-binding Protein Indicating a Novel Mode-of-inhibition PloS One. 2017 | Pubmed ID: 28419165 Charges Shift Protonation: Neutron Diffraction Reveals That Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin Angewandte Chemie (International Ed. in English). 04, 2017 | Pubmed ID: 28371253 Price for Opening the Transient Specificity Pocket in Human Aldose Reductase Upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis ACS Chemical Biology. 05, 2017 | Pubmed ID: 28287700 A False-Positive Screening Hit in Fragment-Based Lead Discovery: Watch out for the Red Herring Angewandte Chemie (International Ed. in English). 02, 2017 | Pubmed ID: 28097765 Occupying a Flat Subpocket in a TRNA-modifying Enzyme with Ordered or Disordered Side Chains: Favorable or Unfavorable for Binding? Bioorganic & Medicinal Chemistry. 10, 2016 | Pubmed ID: 27501913 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. 05, 2016 | Pubmed ID: 27139825 Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study ACS Chemical Biology. 06, 2016 | Pubmed ID: 27028906 An Immucillin-Based Transition-State-Analogous Inhibitor of TRNA-Guanine Transglycosylase (TGT) Chemistry (Weinheim an Der Bergstrasse, Germany). 05, 2016 | Pubmed ID: 26991861 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. Sep, 2015 | Pubmed ID: 26376645 Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin International Journal of Molecular Sciences. Aug, 2015 | Pubmed ID: 26287174 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. Aug, 2015 | Pubmed ID: 25951081 Tracing Binding Modes in Hit-to-lead Optimization: Chameleon-like Poses of Aspartic Protease Inhibitors Angewandte Chemie (International Ed. in English). Feb, 2015 | Pubmed ID: 25630461 Large-scale Mining for Similar Protein Binding Pockets: with RAPMAD Retrieval on the Fly Becomes Real Journal of Chemical Information and Modeling. Jan, 2015 | Pubmed ID: 25474400 Hot-spot Analysis to Dissect the Functional Protein-protein Interface of a TRNA-modifying Enzyme Proteins. Oct, 2014 | Pubmed ID: 24975703 Beyond Affinity: Enthalpy-entropy Factorization Unravels Complexity of a Flat Structure-activity Relationship for Inhibition of a TRNA-modifying Enzyme Journal of Medicinal Chemistry. Jul, 2014 | Pubmed ID: 24960372 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. Jul, 2014 | Pubmed ID: 24955548 Impact of Protein and Ligand Impurities on ITC-derived Protein-ligand Thermodynamics Biochimica Et Biophysica Acta. Sep, 2014 | Pubmed ID: 24792574 Cavities Tell More Than Sequences: Exploring Functional Relationships of Proteases Via Binding Pockets Journal of Chemical Information and Modeling. Aug, 2013 | Pubmed ID: 23834203 Investigation of Specificity Determinants in Bacterial TRNA-guanine Transglycosylase Reveals Queuine, the Substrate of Its Eucaryotic Counterpart, As Inhibitor PloS One. 2013 | Pubmed ID: 23704982 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. 2013 | Pubmed ID: 23534552 Novel Type II Fatty Acid Biosynthesis (FAS II) Inhibitors As Multistage Antimalarial Agents ChemMedChem. Mar, 2013 | Pubmed ID: 23341167 Fingerprint Kernels for Protein Structure Comparison Molecular Informatics. Jul, 2012 | Pubmed ID: 27477463 Targeting the Blind Spot of Polycationic Nanocarrier-based SiRNA Delivery ACS Nano. Nov, 2012 | Pubmed ID: 23036046 Concise and Efficient Syntheses of PreQ1 Base, Q Base, and (ent)-Q Base Organic & Biomolecular Chemistry. Nov, 2012 | Pubmed ID: 23032613 Cofactor-binding Sites in Proteins of Deviating Sequence: Comparative Analysis and Clustering in Torsion Angle, Cavity, and Fold Space Proteins. Feb, 2012 | Pubmed ID: 22095739 Development of Improved PPARβ/δ Inhibitors ChemMedChem. Jan, 2012 | Pubmed ID: 22025402 DSX: a Knowledge-based Scoring Function for the Assessment of Protein-ligand Complexes Journal of Chemical Information and Modeling. Oct, 2011 | Pubmed ID: 21863864 Two Solutions for the Same Problem: Multiple Binding Modes of Pyrrolidine-based HIV-1 Protease Inhibitors Journal of Molecular Biology. Jul, 2011 | Pubmed ID: 21762812 [M2 Inhibitors and Neuraminidase Inhibitors] Pharmazie in Unserer Zeit. Mar, 2011 | Pubmed ID: 21630541 MiniMuDS: a New Optimizer Using Knowledge-based Potentials Improves Scoring of Docking Solutions Journal of Chemical Information and Modeling. Jun, 2011 | Pubmed ID: 21528908 Stereo- and Regioselective Azide/alkyne Cycloadditions in Carbonic Anhydrase II Via Tethering, Monitored by Crystallography and Mass Spectrometry Chemistry (Weinheim an Der Bergstrasse, Germany). May, 2011 | Pubmed ID: 21506176 Superposition and Alignment of Labeled Point Clouds IEEE/ACM Transactions on Computational Biology and Bioinformatics. Nov-Dec, 2011 | Pubmed ID: 21358005 SEGA: Semiglobal Graph Alignment for Structure-based Protein Comparison IEEE/ACM Transactions on Computational Biology and Bioinformatics. Sep-Oct, 2011 | Pubmed ID: 21339532 Fconv: Format Conversion, Manipulation and Feature Computation of Molecular Data Bioinformatics (Oxford, England). Apr, 2011 | Pubmed ID: 21335612 GARLig: a Fully Automated Tool for Subset Selection of Large Fragment Spaces Via a Self-adaptive Genetic Algorithm Journal of Chemical Information and Modeling. Sep, 2010 | Pubmed ID: 20795677 Bidentate Zinc Chelators for Alpha-carbonic Anhydrases That Produce a Trigonal Bipyramidal Coordination Geometry ChemMedChem. Sep, 2010 | Pubmed ID: 20629007 Structure and Substrate Docking of a Hydroxy(phenyl)pyruvate Reductase from the Higher Plant Coleus Blumei Benth Acta Crystallographica. Section D, Biological Crystallography. May, 2010 | Pubmed ID: 20445235 Fragment-based Lead Discovery: Screening and Optimizing Fragments for Thermolysin Inhibition ChemMedChem. Jun, 2010 | Pubmed ID: 20394106 Pyrrolidine Derivatives As Plasmepsin Inhibitors: Binding Mode Analysis Assisted by Molecular Dynamics Simulations of a Highly Flexible Protein ChemMedChem. Mar, 2010 | Pubmed ID: 20112327 How to Replace the Residual Solvation Shell of Polar Active Site Residues to Achieve Nanomolar Inhibition of TRNA-guanine Transglycosylase ChemMedChem. Dec, 2009 | Pubmed ID: 19894214 Secbase: Database Module to Retrieve Secondary Structure Elements with Ligand Binding Motifs Journal of Chemical Information and Modeling. Oct, 2009 | Pubmed ID: 19807134 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. Nov, 2009 | Pubmed ID: 19627989 Structure-based Optimization of Aldose Reductase Inhibitors Originating from Virtual Screening ChemMedChem. May, 2009 | Pubmed ID: 19301313 Evolutionary Construction of Multiple Graph Alignments for the Structural Analysis of Biomolecules Bioinformatics (Oxford, England). Aug, 2009 | Pubmed ID: 19286830 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. Mar, 2009 | Pubmed ID: 19199329 Turns Revisited: a Uniform and Comprehensive Classification of Normal, Open, and Reverse Turn Families Minimizing Unassigned Random Chain Portions Proteins. Feb, 2009 | Pubmed ID: 18704930 Achiral Oligoamines As Versatile Tool for the Development of Aspartic Protease Inhibitors Bioorganic & Medicinal Chemistry. Sep, 2008 | Pubmed ID: 18760609 Computer-aided Design and Synthesis of Nonpeptidic Plasmepsin II and IV Inhibitors ChemMedChem. Sep, 2008 | Pubmed ID: 18752222 Targeting the Open-flap Conformation of HIV-1 Protease with Pyrrolidine-based Inhibitors ChemMedChem. Sep, 2008 | Pubmed ID: 18720485 Structural and Kinetic Analysis of Pyrrolidine-based Inhibitors of the Drug-resistant Ile84Val Mutant of HIV-1 Protease Journal of Molecular Biology. Nov, 2008 | Pubmed ID: 18692068 Development of Benzophenone-based Farnesyltransferase Inhibitors As Novel Antimalarials ChemMedChem. Aug, 2008 | Pubmed ID: 18470859 Studies Addressing the Importance of Charge in the Binding of Fosmidomycin-like Molecules to Deoxyxylulosephosphate Reductoisomerase ChemMedChem. Aug, 2008 | Pubmed ID: 18470849 SFCscore: Scoring Functions for Affinity Prediction of Protein-ligand Complexes Proteins. Nov, 2008 | Pubmed ID: 18442132 Structure-guided Design of C2-symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold Journal of Medicinal Chemistry. Apr, 2008 | Pubmed ID: 18348517 Use of 3D QSAR Models for Database Screening: a Feasibility Study Journal of Chemical Information and Modeling. Feb, 2008 | Pubmed ID: 18211050 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). 2007 | Pubmed ID: 17955562 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. Nov, 2007 | Pubmed ID: 17949745 Thermodynamic Inhibition Profile of a Cyclopentyl and a Cyclohexyl Derivative Towards Thrombin: the Same but for Different Reasons Angewandte Chemie (International Ed. in English). 2007 | Pubmed ID: 17902081 Novel Deoxyxylulosephosphate-reductoisomerase Inhibitors: Fosmidomycin Derivatives with Spacious Acyl Residues Archiv Der Pharmazie. Sep, 2007 | Pubmed ID: 17806130 Saccharin Inhibits Carbonic Anhydrases: Possible Explanation for Its Unpleasant Metallic Aftertaste Angewandte Chemie (International Ed. in English). 2007 | Pubmed ID: 17705204 Use of Biotin Derivatives to Probe Conformational Changes in Proteins The Journal of Biological Chemistry. Jul, 2007 | Pubmed ID: 17545162 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 Binding Journal of Molecular Biology. Jul, 2007 | Pubmed ID: 17524419 Atypical Protonation States in the Active Site of HIV-1 Protease: a Computational Study Journal of Chemical Information and Modeling. Jul-Aug, 2007 | Pubmed ID: 17503762 Crystal Structure of Bacillus Subtilis S-adenosylmethionine:tRNA Ribosyltransferase-isomerase Biochemical and Biophysical Research Communications. Dec, 2006 | Pubmed ID: 17083917 Development, Validation, and Application of Adapted PEOE Charges to Estimate PKa Values of Functional Groups in Protein-ligand Complexes Proteins. Nov, 2006 | Pubmed ID: 16927370 Integrated Approach Using Protein and Ligand Information to Analyze Selectivity- and Affinity-determining Features of Carbonic Anhydrase Isozymes ChemMedChem. Aug, 2006 | Pubmed ID: 16902938 Unexpected Novel Binding Mode of Pyrrolidine-based Aspartyl Protease Inhibitors: Design, Synthesis and Crystal Structure in Complex with HIV Protease ChemMedChem. Jan, 2006 | Pubmed ID: 16892342 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. Jul, 2006 | Pubmed ID: 16688706 A Simple Protocol to Estimate Differences in Protein Binding Affinity for Enantiomers Without Prior Resolution of Racemates Angewandte Chemie (International Ed. in English). Jan, 2006 | Pubmed ID: 16374786 Hydroxyethylene Sulfones As a New Scaffold to Address Aspartic Proteases: Design, Synthesis, and Structural Characterization Journal of Medicinal Chemistry. Oct, 2005 | Pubmed ID: 16220977 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. Nov, 2005 | Pubmed ID: 16206323 An Old Target Revisited: Two New Privileged Skeletons and an Unexpected Binding Mode for HIV-protease Inhibitors Angewandte Chemie (International Ed. in English). May, 2005 | Pubmed ID: 15822136 Successful Virtual Screening for a Submicromolar Antagonist of the Neurokinin-1 Receptor Based on a Ligand-supported Homology Model Journal of Medicinal Chemistry. Oct, 2004 | Pubmed ID: 15481976 Non-thiol Farnesyltransferase Inhibitors: Utilization of the Far Aryl Binding Site by 5-cinnamoylaminobenzophenones Archiv Der Pharmazie. Sep, 2004 | Pubmed ID: 15362122 Non-thiol Farnesyltransferase Inhibitors: N-(4-tolylacetylamino-3-benzoylphenyl)-3-arylfurylacrylic Acid Amides Bioorganic & Medicinal Chemistry. Sep, 2004 | Pubmed ID: 15358286 Crystallographic Study of Inhibitors of TRNA-guanine Transglycosylase Suggests a New Structure-based Pharmacophore for Virtual Screening Journal of Molecular Biology. Apr, 2004 | Pubmed ID: 15050823 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 Design Chembiochem : a European Journal of Chemical Biology. Oct, 2003 | Pubmed ID: 14523925 ZZ Made EZ: Influence of Inhibitor Configuration on Enzyme Selectivity Journal of Molecular Biology. Jul, 2003 | Pubmed ID: 12850145 Crystal Structure of 2-methylisocitrate Lyase (PrpB) from Escherichia Coli and Modelling of Its Ligand Bound Active Centre Journal of Molecular Biology. May, 2003 | Pubmed ID: 12706720 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. Mar, 2003 | Pubmed ID: 12646024 Reconstructing the Binding Site of Factor Xa in Trypsin Reveals Ligand-induced Structural Plasticity Journal of Molecular Biology. Jan, 2003 | Pubmed ID: 12527302 Trypsin Mutants for Structure-based Drug Design: Expression, Refolding and Crystallisation Biological Chemistry. Jul-Aug, 2002 | Pubmed ID: 12437122 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. Sep, 2002 | Pubmed ID: 12213058 Approaches to the Description and Prediction of the Binding Affinity of Small-molecule Ligands to Macromolecular Receptors Angewandte Chemie (International Ed. in English). Aug, 2002 | Pubmed ID: 12203463 PH-dependent Binding Modes Observed in Trypsin Crystals: Lessons for Structure-based Drug Design Chembiochem : a European Journal of Chemical Biology. Mar, 2002 | Pubmed ID: 11921406 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). Sep, 2001 | Pubmed ID: 29712060 Flusso di lavoro e strumenti per lo screening dei frammenti cristallografici presso l'Helmholtz-Zentrum di Berlino Jan Wollenhaupt1, Tatjana Barthel1,2, Gustavo M. A. Lima3, Alexander Metz4, Dirk Wallacher5, Elmir Jagudin3, Franziska U. Huschmann1,4, Thomas Hauß1, Christian G. Feiler1, Martin Gerlach1, Michael Hellmig1, Ronald Förster1, Michael Steffien1, Andreas Heine4, Gerhard Klebe4, Uwe Mueller1, Manfred S. Weiss1 1Macromolecular Crystallography, Helmholtz-Zentrum Berlin, 2Structural Biochemistry Group, Institute for Chemistry and Biochemistry, Freie Universität Berlin, 3BioMAX, MAX IV Laboratory, 4Drug Design Group, Institute of Pharmaceutical Chemistry, Philipps-Universität Marburg, 5Department Sample Environment, Helmholtz-Zentrum Berlin JoVE 62208 Biochemistry
Flusso di lavoro e strumenti per lo screening dei frammenti cristallografici presso l'Helmholtz-Zentrum di Berlino Jan Wollenhaupt1, Tatjana Barthel1,2, Gustavo M. A. Lima3, Alexander Metz4, Dirk Wallacher5, Elmir Jagudin3, Franziska U. Huschmann1,4, Thomas Hauß1, Christian G. Feiler1, Martin Gerlach1, Michael Hellmig1, Ronald Förster1, Michael Steffien1, Andreas Heine4, Gerhard Klebe4, Uwe Mueller1, Manfred S. Weiss1 1Macromolecular Crystallography, Helmholtz-Zentrum Berlin, 2Structural Biochemistry Group, Institute for Chemistry and Biochemistry, Freie Universität Berlin, 3BioMAX, MAX IV Laboratory, 4Drug Design Group, Institute of Pharmaceutical Chemistry, Philipps-Universität Marburg, 5Department Sample Environment, Helmholtz-Zentrum Berlin JoVE 62208 Biochemistry
