The dynamical binding site of HIV integrase:

Julie Schames and I, working in the group of Andy McCammon, discovered a new part of the binding site of the HIV integrase, an enzyme which inserts the viral DNA into the host DNA [14]. This contributed towards the drug discovery efforts of Merck (NSF news story, SDSC news story, AutoDock) whose drug Isentress has been approved by the FDA.

A molecular dynamics simulation of the Shionogi inhibitor bound to integrase induced the opening up of the newly observed "trench". This we detected by docking the Shionogi inhibitor to multiple snapshots of the protein during the simulation. On the left is the inhibitor in the x-ray crystal position used during the simulation. On the right is the inhibitor docked in two additional positions from a simulated structure (the trench is to the right). It can be seen that the active site is quite flexible.