title: Structure-based systems biology for analyzing off-target binding.
abstract: Here off-target binding implies the binding of a small molecule of therapeutic interest to a protein target other than the primary target for which it was intended. Increasingly such off-targeting appears to be the norm rather than the exception, rational drug design notwithstanding, and can lead to detrimental side-effects, or opportunities to reposition a therapeutic agent to treat a different condition. Not surprisingly, there is significant interest in determining a priori what off-targets exist on a proteome-wide scale. Beyond determining putative off-targets is the need to understand the impact of such binding on the complete biological system, with the ultimate goal of being able to predict the phenotypic outcome. While a very ambitious goal, some progress is being made.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, MC9743, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xie
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Philip E
authors.initials: PE
authors.lastname: Bourne
mesh_terms: D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D049490:Systems Biology
chemical_list: D008024:Ligands; D011506:Proteins; D020543:Proteome