Polypharmacology: in silico methods of ligand design and development

Abstract

How to design a ligand to bind multiple targets, rather than to a single target, is the focus of this review. Rational polypharmacology draws on knowledge that is both broad ranging and hierarchical. Computer-aided multitarget ligand design methods are described according to their nested knowledge level. Ligand-only and then receptor–ligand strategies are first described; followed by the metabolic network viewpoint. Subsequently strategies that view infectious diseases as multigenomic targets are discussed, and finally the disease level interpretation of medicinal therapy is considered. As yet there is no consensus on how best to proceed in designing a multitarget ligand. The current methodologies are bought together in an attempt to give a practical overview of how polypharmacology design might be best initiated.