Figure 1. Structure-based drug discovery workflow.

All of the available PH domain 3D structures in the PDB were used to build our PSSM scoring functions which were employed to construct the homology model of GAB1 PH domain. The derived structure was used to perform high-throughput virtual screening of five million drug/lead-like compounds. Through a funnel-like process 20 hits were selected for experimental testing and five were confirmed as consistently active in all of the assays.