We have shown that our newly developed Monte Carlo method -Molecular Dartingallows reversible sampling of specific binding We can see in this example that the ligand position is quite near the reference pose. (e) shows the same system in (d ) but after the MolDarting move takes place. (f ) shows the same system in (e) but using the previous representation found in (a-c). The VDW representation of the ligand in (f ) helps visualize some new clashes present after MolDarting that will need to be resolved before the ligand is fully interacting. g shows the system after the ligand has full steric interactions. Here we can see there is a sizable reorientation of the ligand in the binding site. In (h) the ligand's electrostatic and steric interactions are restored, and the protocol work accumulated is then used to accept or reject these new positions as shown here.