Fig. 3
From: Large-scale computational drug repositioning to find treatments for rare diseases
Flowchart of the drug repositioning procedure devised in this study. For protein sequences from DrugBank and Orphanet (a), template-based structure modeling is conducted with eThread to construct 3D models (b). Protein models are subsequently annotated by eFindSite with drug-binding sites (c). A similarity-based ligand docking is performed for DrugBank drug-protein pairs, i.e., a globally similar template is aligned onto the target structure with Fr-TM-align and then the drug is aligned onto the template-bound ligand with KCOMBU (d). The modeling procedure produces drug-bound structures for DrugBank and unbound structures for Orphanet proteins (e). Next, all-against-all matching of drug-binding pockets in DrugBank and Orphanet proteins is conducted with eMatchSite (f). The DrugBank compound is transferred to the Orphanet model when the similarity of binding pockets is sufficiently high and the resulting complex is refined (g). Finally, the quality of final Orphanet complex models is assessed with DFIRE and virtual screening (h)
