Molecular docking programs successfully predict the binding of a β-lactamase inhibitory protein to TEM-1 β-lactamase

Crystallization of the 1:1 molecular complex between the β-lactamase TEM-1 and the β-lactamase inhibitory protein BLIP has provided an opportunity to put a stringent test on current protein-docking algorithms. Prior to the successful determination of the structure of the complex, nine laboratory groups were given the refined atomic coordinates of each of the native molecules. Other than the fact that BLIP is an effective inhibitor of a number of β-lactamase enzymes (KI for TEM-1∼100 pM) no other biochemical or structural data were available to assist the practitioners in their molecular docking. In addition, it was not known whether the molecules underwent conf ormational changes upon association or whether the inhibition was competitive or non-competitive. All six of the groups that accepted the challenge correctly predicted the general mode of association of BLIP and TEM-1.