Reverse docking: a powerful tool for drug repositioning and drug rescue

Abstract

Reverse or inverse docking is proving to be a powerful tool for drug repositioning and drug rescue. It involves docking a small-molecule drug/ligand in the potential binding cavities of a set of clinically relevant macromolecular targets. Detailed analyses of the binding characteristics lead to ranking of the targets according to the tightness of binding. This process can potentially identify novel molecular targets for the drug/ligand which may be relevant for its mechanism of action and/or side effect profile. Another potential application of reverse docking is during the lead discovery and optimization stages of the drug-discovery cycle. This review summarizes the state-of-the-art and future prospects of the reverse docking with particular emphasis on computational molecular design.