Gerhard Klebe

Price for Opening the Transient Specificity Pocket in Human Aldose Reductase upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis.

pH-dependent binding modes observed in trypsin crystals: lessons for structure-based drug design.

Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors.

DrugScore meets CoMFA: adaptation of fields for molecular comparison (AFMoC) or how to tailor knowledge-based pair-potentials to a particular protein.

Trypsin mutants for structure-based drug design: expression, refolding and crystallisation.

Reconstructing the binding site of factor Xa in trypsin reveals ligand-induced structural plasticity.

Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis.

Crystal structure of 2-methylisocitrate lyase (PrpB) from Escherichia coli and modelling of its ligand bound active centre.

ZZ made EZ: influence of inhibitor configuration on enzyme selectivity.

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.

Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening.

Non-thiol farnesyltransferase inhibitors: N-(4-tolylacetylamino-3-benzoylphenyl)-3-arylfurylacrylic acid amides.

Non-thiol farnesyltransferase inhibitors: utilization of the far aryl binding site by 5-cinnamoylaminobenzophenones.

Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model.

An old target revisited: two new privileged skeletons and an unexpected binding mode for HIV-protease inhibitors.

Mechanism and substrate specificity of tRNA-guanine transglycosylases (TGTs): tRNA-modifying enzymes from the three different kingdoms of life share a common catalytic mechanism.

Hydroxyethylene sulfones as a new scaffold to address aspartic proteases: design, synthesis, and structural characterization.

A simple protocol to estimate differences in protein binding affinity for enantiomers without prior resolution of racemates.

An efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS coronavirus main protease (SARS-CoV Mpro) inhibitors.

Unexpected novel binding mode of pyrrolidine-based aspartyl protease inhibitors: design, synthesis and crystal structure in complex with HIV protease.

Integrated approach using protein and ligand information to analyze selectivity- and affinity-determining features of carbonic anhydrase isozymes.

Development, validation, and application of adapted PEOE charges to estimate pKa values of functional groups in protein-ligand complexes.

Crystal structure of Bacillus subtilis S-adenosylmethionine:tRNA ribosyltransferase-isomerase.

Atypical protonation states in the active site of HIV-1 protease: a computational study.

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.

Use of biotin derivatives to probe conformational changes in proteins.

Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste.

Novel deoxyxylulosephosphate-reductoisomerase inhibitors: fosmidomycin derivatives with spacious acyl residues.

Thermodynamic inhibition profile of a cyclopentyl and a cyclohexyl derivative towards thrombin: the same but for different reasons.

Glutamate versus glutamine exchange swaps substrate selectivity in tRNA-guanine transglycosylase: insight into the regulation of substrate selectivity by kinetic and crystallographic studies.

KNOBLE: a knowledge-based approach for the design and synthesis of readily accessible small-molecule chemical probes to test protein binding.

Use of 3D QSAR models for database screening: a feasibility study.

Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold.

SFCscore: scoring functions for affinity prediction of protein-ligand complexes.

Studies addressing the importance of charge in the binding of fosmidomycin-like molecules to deoxyxylulosephosphate reductoisomerase.

Development of benzophenone-based farnesyltransferase inhibitors as novel antimalarials.

Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease.

Turns revisited: a uniform and comprehensive classification of normal, open, and reverse turn families minimizing unassigned random chain portions.

Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based inhibitors.

Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors.

Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors.

Crystal structure analysis and in silico pKa calculations suggest strong pKa shifts of ligands as driving force for high-affinity binding to TGT.

Evolutionary construction of multiple graph alignments for the structural analysis of biomolecules.

Structure-based optimization of aldose reductase inhibitors originating from virtual screening.

An integrative approach combining noncovalent mass spectrometry, enzyme kinetics and X-ray crystallography to decipher Tgt protein-protein and protein-RNA interaction.

Secbase: database module to retrieve secondary structure elements with ligand binding motifs.

How to replace the residual solvation shell of polar active site residues to achieve nanomolar inhibition of tRNA-guanine transglycosylase.

Pyrrolidine derivatives as plasmepsin inhibitors: binding mode analysis assisted by molecular dynamics simulations of a highly flexible protein.

Fragment-based lead discovery: screening and optimizing fragments for thermolysin inhibition.

Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plant Coleus blumei Benth.

Bidentate Zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry.

GARLig: a fully automated tool for subset selection of large fragment spaces via a self-adaptive genetic algorithm.

fconv: Format conversion, manipulation and feature computation of molecular data.

SEGA: semiglobal graph alignment for structure-based protein comparison.

Superposition and alignment of labeled point clouds.

Stereo- and regioselective azide/alkyne cycloadditions in carbonic anhydrase II via tethering, monitored by crystallography and mass spectrometry.

MiniMuDS: a new optimizer using knowledge-based potentials improves scoring of docking solutions.

[M2 inhibitors and neuraminidase inhibitors].

Two solutions for the same problem: multiple binding modes of pyrrolidine-based HIV-1 protease inhibitors.

DSX: a knowledge-based scoring function for the assessment of protein-ligand complexes.

Development of improved PPARβ/δ inhibitors.

Cofactor-binding sites in proteins of deviating sequence: comparative analysis and clustering in torsion angle, cavity, and fold space.

Concise and efficient syntheses of preQ1 base, Q base, and (ent)-Q base.

Targeting the blind spot of polycationic nanocarrier-based siRNA delivery.

Novel type II fatty acid biosynthesis (FAS II) inhibitors as multistage antimalarial agents.

Launching spiking ligands into a protein-protein interface: a promising strategy to destabilize and break interface formation in a tRNA modifying enzyme.

Investigation of specificity determinants in bacterial tRNA-guanine transglycosylase reveals queuine, the substrate of its eucaryotic counterpart, as inhibitor.

Cavities tell more than sequences: exploring functional relationships of proteases via binding pockets.

Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

Chasing protons: how isothermal titration calorimetry, mutagenesis, and pKa calculations trace the locus of charge in ligand binding to a tRNA-binding enzyme.

Beyond affinity: enthalpy-entropy factorization unravels complexity of a flat structure-activity relationship for inhibition of a tRNA-modifying enzyme.

Hot-spot analysis to dissect the functional protein-protein interface of a tRNA-modifying enzyme.

Large-scale mining for similar protein binding pockets: with RAPMAD retrieval on the fly becomes real.

Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors.

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.

Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin.

Thermodynamics of protein-ligand interactions as a reference for computational analysis: how to assess accuracy, reliability and relevance of experimental data.

An Immucillin-Based Transition-State-Analogous Inhibitor of tRNA-Guanine Transglycosylase (TGT).

Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study.

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

Fingerprint Kernels for Protein Structure Comparison.

Occupying a flat subpocket in a tRNA-modifying enzyme with ordered or disordered side chains: Favorable or unfavorable for binding?

A False-Positive Screening Hit in Fragment-Based Lead Discovery: Watch out for the Red Herring.

Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin.

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.

From Structure to Function: A New Approach to Detect Functional Similarity among Proteins Independent from Sequence and Fold Homology.

Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase.

Paradoxically, Most Flexible Ligand Binds Most Entropy-Favored: Intriguing Impact of Ligand Flexibility and Solvation on Drug-Kinase Binding.

Swapping Interface Contacts in the Homodimeric tRNA-Guanine Transglycosylase: An Option for Functional Regulation.

Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase.

On the Implication of Water on Fragment-to-Ligand Growth in Kinase Binding Thermodynamics.

Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes.

Strategies for Late-Stage Optimization: Profiling Thermodynamics by Preorganization and Salt Bridge Shielding.

Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction.

Protein-Ligand Complex Solvation Thermodynamics: Development, Parameterization, and Testing of GIST-Based Solvent Functionals.

Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.

Role of Water Molecules in Protein-Ligand Dissociation and Selectivity Discrimination: Analysis of the Mechanisms and Kinetics of Biomolecular Solvation Using Molecular Dynamics.

The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II.

A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II.

F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening.

Fragment-Based Discovery of Non-bisphosphonate Binders of Trypanosoma brucei Farnesyl Pyrophosphate Synthase.

Fragment Binding to Kinase Hinge: If Charge Distribution and Local pK Shifts Mislead Popular Bioisosterism Concepts.

Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.

The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase.

Advancing GIST-Based Solvent Functionals through Multiobjective Optimization of Solvent Enthalpy and Entropy Scoring Terms.

How a Fragment Draws Attention to Selectivity Discriminating Features between the Related Proteases Trypsin and Thrombin.