Structure-based Rational Drug Development
The structure-based drug design enables the rational design of lead compounds. The atomic-resolution structures are used to guide the design. Structure-based methodology has contributed to the development of many therapeutic agents, such as Inhibitors of HIV protease, Abl kinase (Imatinib) or Bcl-2 proteins.
X-ray crystallography and NMR spectroscopy are used here to determine the structure of the target protein, identify pharmacophores and obtain structure-activity relationship data. Active molecules are found by in silico screening or de novo design. Hits from high-throughput screens (HTS) (e. g, based on in vitro binding assays such as fluorescence polarization, AlphaScreen, etc.) are validated by crystallographic analysis and NMR. Fragment-based screening by NMR is established at HMGU and FMP. In the network of Helmholtz centres (HMGU, HZI, FZJ, MDC/FMP) a unique and international competitive infrastructure and expertise is available to support structural biology and structure-based drug discovery.