GPCR Drug Discovery
The group is focused on the functionality of G-protein-coupled receptors (GPCRs) within the context of CNS-related disorders, taking into account: receptor plasticity, activation mechanism, signalling bias, ligand binding, the effect of the membrane and other interaction partners. The ultimate goal is to translate the molecular insights obtained into the design of drug candidates with improved therapeutic profiles.
The main research lines are:
• In-silico Multi-Receptor Profiling of Antipsychotic Drugs, focusing on deciphering the molecular mechanisms of this complex interplay of current antipsychotic drugs that are responsible for their clinical efficacies.
• GPCR Dimers as a Drug Target for the Treatment of Schizophrenia. Our group provides support for the design of bivalent ligands that selectively target a specific GPCR dimer. Once a target is validated, we apply diverse computational tools to obtain first small drug-like molecules towards this target.
• Membrane Lipid-Mediated Effects on GPCR signalling by studying direct and indirect membrane effects on receptor monomers and dimers using all-atom as well as coarse-grained simulation setups.
• Database for GPCR dynamics. The main mission of this project is to provide dynamic insights into crystallized receptors at a publicly accessible platform.
• Stepniewski T, Torrens M, Rodríguez-Espigares I, Giorgino T, Primdahl KG, Vik A, Stenstrøm Y, Selent J, Hansen TV. Synthesis, molecular modelling studies and biological evaluation of new oxoeicosanoid receptor 1 agonists. Bioorgan Med Chem 2018; 26(12): 3580-3587. IF 2.881. Q2.
Ongoing Research Projects
• La modulación alostérica del receptor D2 de la dopamina forma parte del mecanismo de acción del litio: de la evidencia molecular a la neuroimagen funcional
- Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00460)
- Period: from 2016 to 2019
- Principal investigator: Selent, Jana
• Rodríguez-Espigares I. GPCRmd - A web platform for collection, visualization and analysis of molecular dynamics data for G protein-coupled receptors: Bridging the gap between receptor dynamics and receptor functionality. Universitat Pompeu Fabra.
- Director: Selent, Jana; Sanz Carreras, Ferran
- Date of defense: 04/04/2018
• Kaczor AA, Bartuzi D, Stepniewski TM, Matosiuk D, Selent J. Protein-Protein Docking in Drug Design and Discovery. Methods Mol Biol, 2018; 1762: 285-305.