Local Alignment of Ligand Binding Sites in Proteins for Polypharmacology and Drug Repositioning

The administration of drugs is a key strategy in pharmacotherapy to treat diseases. Drugs are typically developed to modulate the function of specific proteins, which are directly associated with particular disease states. Nonetheless, recent studies suggest that protein-drug interactions are rather promiscuous and the majority of pharmaceuticals exhibit activity against multiple, often unrelated proteins. Certainly, the lack of selectivity often leads to drug side effects; on the other hand, these polypharmacological attributes can be used to develop drugs acting on multiple targets within a unique disease pathway, as well as to identify new targets for existing drugs, which is known as drug repositioning. To support drug development and repurposing, we developed eMatchSite, a new approach to detect those binding sites having the capability to bind similar compounds. eMatchSite is available as a standalone software and a webserver at http://www.brylinski.org/ematchsite .