Until now, the overarching goal of GCMC and GCNCMC has been to sample the binding and unbinding of tightly bound water molecules in buried protein regions where regular MD may otherwise struggle within a reasonable time scale. In much the same vein, simulations of ligand binding are also hampered by the relative time scales over which ligands exchange between a protein and solvent. To this end, we have further extended GCNCMC to sample the binding of small molecules to proteins where the induced fit mechanism is even more crucial. Note that by default we use the combined GCNCMC method for the sampling of small molecules as the acceptance rates of instantaneous GCMC moves are prohibitively low. We aim to demonstrate the application of GCNCMC to FBDD, addressing three of the aforementioned goals of in silico structure-based drug design: finding potential binding sites, identifying fragment binding modes, and predicting binding affinities. Conceptually, the method is almost identical to GCNCMC water sampling with few modifications, and for more details, we refer the reader to the "Methods" section, and Supplementary Information, where the theoretical basis is outlined in depth.