Objectif Once a new drug target is discovered, screening techniques are applied to detect prospective hits. However, which hit should be taken to the next level of development? This decision is most crucial as it entails huge financial commitments of the subsequent drug optimization. In consequence drugs are only developed against diseases that promise short-term profit. Chemogenomic profiling allows to compile parameters characterizing binding of drug candidates that achieve optimal interference with protein function. Membrane proteins demand different properties than viral ones. Either high isoform selectivity, promiscuous family-wide binding or efficient resistance tolerance is desired. This calls for very different ligand binding characteristics, requiring either enthalpy-/entropy-driven binding, rigid shape complementarity or pronounced residual mobility at the binding site. Interaction kinetics determine on/off-rates and the time a drug spends with its target. Their correct adjustment is essential for drug efficacy. At present chemogenomic binding parameters are rarely available and their correlation with the required target properties is hardly understood. We want to compile a knowledge base from congeneric protein-ligand series to correlate structural, thermodynamic, interaction-kinetic and dynamic behaviour to predict the qualities a lead must meet to optimally address a target. Our studies involve crystal structure analyses, microcalorimetry, molecular dynamics simulations, site-directed mutagenesis and interaction kinetics. This provides a comprehensive picture to productively change our current understanding of drug-protein binding to move from a current trial-and-error to a more efficient rational approach. It provides the opportunity to also consider orphan drugs and address neglected diseases. Champ scientifique medical and health sciencesbasic medicinepharmacology and pharmacydrug discoveryengineering and technologymaterials engineeringcrystalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Appel à propositions ERC-2010-AdG_20100317 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil PHILIPPS UNIVERSITAET MARBURG Contribution de l’UE € 1 754 615,28 Adresse BIEGENSTRASSE 10 35037 Marburg Allemagne Voir sur la carte Région Hessen Gießen Marburg-Biedenkopf Type d’activité Higher or Secondary Education Establishments Chercheur principal Gerhard Friedrich Klebe (Prof.) Contact administratif Lois Woestman (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire PHILIPPS UNIVERSITAET MARBURG Allemagne Contribution de l’UE € 1 754 615,28 Adresse BIEGENSTRASSE 10 35037 Marburg Voir sur la carte Région Hessen Gießen Marburg-Biedenkopf Type d’activité Higher or Secondary Education Establishments Chercheur principal Gerhard Friedrich Klebe (Prof.) Contact administratif Lois Woestman (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée