Leadhopping – and beyond

Abstract

Structural novelty has depended for its discovery on a combination of experimental and virtual screening, where virtual screening has meant either docking into a receptor or pharmacophoric or two-dimensional similarity. In this review, leadhopping denotes a new, far more convenient and apparently quite as effective, set of virtual screening methods, all of which emphasise a much more detailed similarity in ligand shape than the pharmacophore approach. Furthermore, some of these leadhopping methods have been adapted to address much broader needs, such as accelerated and simplified lead optimisation, access to an unprecedented vast structural space, and even useful forecasts of off-target pharmacological effects in humans. These methods seem robust and automatable enough to be used directly by laboratory chemists.

Keywords::

• dbtop
• leadhopping
• molecular similarity
• ROCS
• scaffold hopping
• shape similarity
• Surflex
• topomer