Inhibitors of protein-protein interactions: new methodologies to tackle this challenge.

Several advances in the fields of crystallography, molecular modeling, biophysical assays and chemistry are converging to making protein-protein interaction targets more amenable to drug design. These include steps towards improving crystallization of protein-protein complexes, identifying the clusters of residues that constitute putative small molecule binding 'hot spots', generating new methods for detecting the binding of small molecules to target proteins, and generating custom libraries via diversity oriented synthesis to enable the identification of natural-product-like hits.