MD simulations of the spontaneous unbinding of a millimolar inhibitor of FKBP

The movie shows a smoothed MD trajectory of a small molecule unbinding from the protein FKBP. The inhibitor molecule is shown in yellow with its ketone and hydroxyl oxygen atoms in red. The protein is shown in Cartoon representation (pink) with residues important to binding highlighted as sticks (coloring by atom type). These are mostly aromatic residues in addition to a prominent aspartic acid. Green dashed lines indicate the formation and breakage of transient hydrogen bonds between small molecule and protein. Initially the small molecule inhibitor explores a number of different conformations in the binding site (including a full flip). Unbinding occurs first at ca. 35sec and is followed by transient rebinding before full dissociation occurs at ca. 50sec.