Promiscuous Ligands from Experimentally Determined Structures, Binding Conformations, and Protein Family-Dependent Interaction Hotspots.

ABSTRACT: Compound promiscuity is often attributed to nonspecific binding or assay artifacts. On the other hand, it is well-known that many pharmaceutically relevant compounds are capable of engaging multiple targets in vivo, giving rise to polypharmacology. To explore and better understand promiscuous binding characteristics of small molecules, we have searched X-ray structures (and very few qualifying solution structures) for ligands that bind to multiple distantly related or unrelated target proteins. Experimental structures of a given ligand bound to different targets represent high-confidence data for exploring promiscuous binding events. A total of 192 ligands were identified that formed crystallographic complexes with proteins from different families and for which activity data were available

SUBMITTER: Gilberg E 

PROVIDER: S-EPMC6648413 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature