Structure-based drug design characterization

Most protein-protein binding energies are related only to a group of a few amino acids at intermolecular protein interfaces the hot spots. The characterization of the energetics of molecular complexes, especially the detection of these hot spots is essential to structure-based drug design. 

Importantly, the choice of CADD methods which may be applicable directly to drug design exclusively depends upon the availability of actual viable receptor information(s). In fact, the structure-based drug design proves to be of great help provided the ensuing receptor structure has been carefully and meticulously characterized by either high-resolution NMR-spectroscopy or X-ray... 

Recently, fragment based drug design (FBDD) has emerged as a popular structure based approach to lead discovery. Despite the success of FBDD for myriad proteins, the thermodynamic basis for its success remains elusive. Using stromelysin-1 (MMP-3) as a model system and two previously described ligands, we have characterized extensively the thermodynamic principles of additivity and cooperativity in the context of FBDD. The results of these studies and their implications for drug discovery will be discussed. 

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