GBPM: GRID based pharmacophore model. Concept and application studies to protein-protein recognition

Motivation: Automatic procedures to obtain pharmacophore models from experimentally determined macromolecular complexes can help in the drug discovery process, especially when protein–protein recognition plays an important biological role. Results: The GRID-based pharmacophore model (GBPM) is a fully objective method for defining most relevant interaction areas in complexes deriving pharmacophore models from three-dimensional (3D) molecular structure information. It is based on logical and clustering operations with3Dmapscomputedby theGRIDprogramonstructurally known molecular complexes. In this manuscript we describe the concept and discuss application examples regarding protein–protein recognition. In particular two complexes selected in the Protein Data Bank have been tested to evaluate the GBPM capability to identify interaction areas. The results obtained show the capabilities of this new bioinformatic method.