MIDAS represents the first computational methodology for the identification of ABSs in GPCRs. Notably, the approach proved to be successful in all known scenarios, including the most challenging case where the AM binds at the interface between the receptor and the cellular membrane. MIDAS relies upon a fully automatized pipeline that spans from fragment identification to result analysis. To this aim, ad hoc protocols for membrane-protein systems probe-mapping MD simulation have been developed and thoroughly tested. In particular, the combination of such protocols and the use of fragments instead of standard co-solvents enables to overcome current limitations of co-solvent MD-mapping such as probe non-specific binding and/or low sampling, protein denaturation, and membrane distortion. MIDAS technology outperforms any other existing strategy based on co-solvent mapping and is able to identify ABSs in simulation times as short as 20 ns. FBDD is nowadays being intensively applied in drug discovery through cost-intensive NMR campaigns, thus being suitable mostly for soluble drug targets and not yet routinely applicable to membrane proteins like GPCRs. As the first approach computationally enabling FBDD for GPCRs, MIDAS has the potential to foster the development of novel health technologies for the discovery of safer drugs targeting membrane proteins. To this aim, MIDAS has already achieved a significant breakthrough by identifying a previously unknown ABS in the 5HT2CR, thus paving the way for the development of novel safer anti-obesity drugs acting via a different mechanism with respect to the clinically approved drug locanserin.
