Graph-based similarity concepts in virtual screening

Applying similarity for finding new promising compounds is a key issue in drug design. Conversely, quantifying similarity between molecules has remained a difficult task despite the numerous approaches. Here, some general aspects along with recent developments regarding similarity criteria are collected. For the purpose of virtual screening, the compounds have to be encoded into a computer-readable format that permits a comparison, according to given similarity criteria, comprising the use of the 3D structure, fingerprints, graph-based and alignment-based approaches. Whereas finding the most common substructures is the most obvious method, more recent approaches take into account chemical modifications that appear throughout existing drugs, from various therapeutic categories and targets.