For B3-10, the minimum energy penalty arising from the restraints for setting a θ A or θ B to 0 or 180 degrees was approximately 5 k B T , meaning that collinearity was relatively likely and crashes may have been anticipated. However, for B2-10, the minimum penalty for collinearity was approximately 10 k B T . This makes crashes in the decoupled state highly unlikely, but when the ligand is still interacting with the protein it may become trapped in unusual orientations which distort the anchor points towards collinearity. This was the cause of the crash for B3-10 run 1: during the vanish λ = 0.475 window the simulation failed after θ A approaches 0 (Figure ). This occurred because the ligand became trapped underneath the terminal proline residue, resulting in θ A approaching collinearity. A better restraint Snapshots taken from run 1 at 1.12 ns (upper image) and 5.30 ns (lower image). Windows rendered with PyMOL. selection algorithm would have discounted restraints if the energy penalty from the restraints for collinearity was below some threshold, rather than only checking the equilibrium angles.