title: Modeling approaches for ligand-based 3D similarity.
abstract: 3D ligand-based similarity approaches are widely used in the early phases of drug discovery for tasks such as hit finding by virtual screening or compound design with quantitative structure-activity relationships. Here in we review widely used software for performing such tasks. Some techniques are based on relatively mature technology, shape-based similarity for instance. Typically, these methods remained in the realm of the expert user, the experienced modeler. However, advances in implementation and speed have improved usability and allow these methods to be applied to databases comprising millions of compounds. There are now many reports of such methods impacting drug-discovery projects. As such, the medicinal chemistry community has become the intended market for some of these new tools, yet they may consider the wide array and choice of approaches somewhat disconcerting. Each method has subtle differences and is better suited to certain tasks than others. In this article we review some of the widely used computational methods via application, provide straightforward background on the underlying theory and provide examples for the interested reader to pursue in more detail. In the new era of preclinical drug discovery there will be ever more pressure to move faster and more efficiently, and computational approaches based on 3D ligand similarity will play an increasing role in in this process.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Janssen-Cilag S A, Calle Jarama 75, Poligono Industrial, 45007 Toledo, Spain. gtresade@its.jnj.com
authors.forename: Gary
authors.initials: G
authors.lastname: Tresadern
authors.forename: Daniele
authors.initials: D
authors.lastname: Bemporad
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D008024:Ligands