Research line

Starting from our deep understanding of the GPCR signaling systems, and our current structure-based computational tools for the design of modulators of these receptors, this research line focuses on further methodological developments that allow us to tackle allosteric binding sites and develop agonists that stabilize particular conformations of the receptor. For the former, we have developed a pipeline to localize allosteric binding sites, bench-marked it on GPCRs with known allosteric modulators and applied it on a prospective project in collaboration with a CRO for a particular target. For the biassed signaling branch of the project, we make use of our representation of GPCR activation via thermodynamic cycles, solved by FEP simulations (See Jespers et al., PlOS, 2021). Both sides of the project are conducted in collaboration with chemistry groups from the industry or academia.