title: Structural systems pharmacology: the role of 3D structures in next-generation drug development.
abstract: Structural systems pharmacology offers a novel way of approaching drug discovery by considering the global physiological environment of protein targets, and the effects derived of tinkering with them, without losing the key molecular details. In this article, we review some recent advances in the structural annotation of cell networks and discuss their potential impact on some of the hottest areas of drug development. In particular, we analyze recent structure-based strategies to target networks, protein interaction interfaces and allosteric sites, and how they will help in the development of more potent and specific treatments. Finally, we propose that mapping genetic variations onto protein networks, beyond the pharmacological targets, can rationalize interindividual variability in drug response, giving valuable hints to advance toward personalized medicine.
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Institute for Research in Biomedicine-IRB Barcelona, c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Duran-Frigola
authors.forename: Roberto
authors.initials: R
authors.lastname: Mosca
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods; D057285:Precision Medicine / Q000379:methods; D060066:Protein Interaction Maps / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins