Research in F. Fanelli lab. has historically focused on the development of computational protocols and structural models to decipher the functioning mechanisms of G protein-coupled receptors (GPCRs) of the rhodopsin family and their cognate Gα proteins. More recently the interests have extended to the small G proteins of the Ras GTPase superfamily, in particular RhoA and its activators, i.e. the Guanine Exchange Factors (GEF) of the Dbl family.
Essential aspects of the research include development of protocols and software for tertiary and quaternary protein structure predictions and for the analyses of biomolecular structures and trajectories. Other relevant branches concern structure-based drug discovery/design. Recent developments involve also the integration of atomistic and network-level (Systems Biology) simulations to unveil the structural determinants of mutations linked to retinal diseases.
Major ongoing projects
- Integrated in silico and in vitro studies towards the characterization of rhodopsin mutations associated with the Autosomal Dominant form of Retinitis Pigmentosa (ADRP);
- structure-based discovery/development of pharmacological chaperones with therapeutic potential against ADRP caused by rhodopsin mutations;
- structure-based discovery/development of inhibitors of Lbc-RhoA interaction with therapeutic potential as anticancer agents;
- structure-based discovery of V2 vasopressin receptor ligands as potential therapeutic agents against the Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD);
- structure-based discovery of small ligands of the KDEL receptor;
- atomistic and network simulations of transducin mutations associated with retinal diseases;
- investigation of Gα protein activation by mutations and their GEFs;
- unveiling the functional dynamics of RhoA and RhoGEFs of the Dbl family;
- structure predictions of the architecture of GPCR dimers/oligomers and of GPCR-G protein complexes;
- development of the Protein Structure Network (PSN) analysis tool to unveil the structural communication in biomolecular systems: Family A GPCRs, Ras GTPases, and Dbl family GEFs as main subjects;
- implementation of a mixed PSN and Elastic Network Model approach onto the and maintenance of the WebPSN server for predicting the structural communication in biosystems;
- maintenance and development of the Wordom software for the analysis of molecular structures, trajectories, and free energy surfaces.