Objetivo 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. Ámbito científico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoveryengineering and technologymaterials engineeringcrystalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programa(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) Tema(s) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2010-AdG_20100317 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida PHILIPPS UNIVERSITAET MARBURG Aportación de la UE € 1 754 615,28 Dirección BIEGENSTRASSE 10 35037 Marburg Alemania Ver en el mapa Región Hessen Gießen Marburg-Biedenkopf Tipo de actividad Higher or Secondary Education Establishments Investigador principal Gerhard Friedrich Klebe (Prof.) Contacto administrativo Lois Woestman (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo PHILIPPS UNIVERSITAET MARBURG Alemania Aportación de la UE € 1 754 615,28 Dirección BIEGENSTRASSE 10 35037 Marburg Ver en el mapa Región Hessen Gießen Marburg-Biedenkopf Tipo de actividad Higher or Secondary Education Establishments Investigador principal Gerhard Friedrich Klebe (Prof.) Contacto administrativo Lois Woestman (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos