ESR14: David Sotillo Núñez
University of Urbino, Italy
Dipartimento di Scienze Biomolecolari (DISB)
Prof. Giovanni Bottegoni
Allosteric modulation of GPCRs at the protein-membrane interface
Membrane components have recently been characterized as important regulators of membrane protein activity. Lipids exert these effects by directly and specifically binding to the protein surface, rather than simply modifying the bilayer biophysical properties. Here, we aim at:
1) Systematically characterizing putative binding hot-spots for membrane components (e.g., cholesterol, PIP2, etc.) in GPCRs by specifically adapting to the task at hand a multiscale protocol which we have previously reported (Ferraro et al., Plos ONE 2016).
2) Then, we will target these putative binding sites in virtual ligand screening campaigns. This goal is particularly innovative as we attempt to find drug-like compounds displaying affinity for pockets evolved to lodge lipids (Fu, Bottegoni, et al. Nat Neuroscience 2011).
1) Systematic characterization of binding sites for membrane components (e.g., cholesterol, PIP2, etc.) at the protein–membrane interface in GPCRs.
2) Identification of novel PAMs, NAMs, or SAMs by targeting pockets characterized in (1).
Brief Scientific Bio
I began my studies in the field of Biochemistry at the Universitat Autònoma de Barcelona (Barcelona, Spain), where I discovered for the first time the possibility of combining my two passions, namely biosciences and technology, when I took the bioinformatics and structural biology modules on the last year of my bachelor’s degree. Therefore, I enrolled in the Bioinformatics for Health Sciences master program at the Universitat Pompeu Fabra (Barcelona, Spain). In my master’s thesis I developed an automated pipeline to detect and analyze lateral channels in GPCRs, from which ligands, and sometimes lipids, can reach the binding sites squeezing between transmembrane helices. My previous experience in molecular dynamics simulations and in handling of the resulting trajectories through Python programming were instrumental in joining the University of Urbino (Urbino, Italy) as an ESR in the ALLODD project, under the supervision of Prof. Giovanni Bottegoni.