Molecular Modelling in Drug Design

1. LABORATORY FOR BIOMOLECULAR MODELLING Molecular Modelling in Drug Design • The application of computational techniques in the development of new drugs: computer aided or structure baseddrug design. • A modeller is an interdisciplinairy scientist who incorporates chemical, biochemical and farmaceutical knowledge into computational models. • Our laboratory uses these methods for drug design and to develop new methods. • Close colaboration with chemical and biochemical laboratories. Methods in Computional Drug Design Molecular docking 3D-QSAR/QSPR • Molecular docking is the simulation of the binding of a drug to a protein. • The output are binding conformations and a score (the calculated energy of binding). • The best scoring molecules are the potential inhibitors. • A 3D-QSAR model is the generation of a mathematical formula which predicts activity. • The essential step is the superposition of the molecules. • This superposition also gives a projected image of the binding site in the proteins. pharmacophoric modelling . . Virtual Screening SmiGeL • Pharmacophore models do not represent molecules but the essential features for biological activity. • These simplifyed models allow us to quickly scan a database of molecules. • Receptor based pharmacophores are a new goal for structure based drug design. • Virtual screening is the application of previous methods on a virtual database of molecules. • A major problem is the construction of a virtual library. • Development of SmiGeL which quickly generates a library based on a scaffold molecule.