modes/conformations by constructing darting moves based on the internal and external degrees of freedom of a ligand. This allows reversible hops between pre-defined metastable binding modes or conformations, opening up exciting new possibilities. Molecular Darting worked well in improving sampling of the different binding modes/conformations in the simpler model systems we considered, and notably showed marked improvements in sampling compared to uniform Monte Carlo sampling methods and plain Molecular Dynamics. We did experience challenges, however, in getting acceptance of MolDarting moves in combination with NCMC in the HIV integrase system. Even though the NCMC/MolDarting moves were not accepted, we did find that the attempted MolDarting move proposals were into the intended binding sites/binding modes.