Structural Systems Pharmacology: the role of 3D structures in next generation drug development

Duran-Frigola M, Mosca R, Aloy P,
Chemistry & Biology, 2013, 20(5), 674-684

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 manuscript 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 analyse 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 suggest how mapping genetic variations onto pharmacological targets can rationalize interindividual variability in drug response, giving valuable hints to advance towards personalized medicine.