MOLECULAR DOCKING PROGRAMS SUCCESSFULLY PREDICT THE BINDING OF A BETA-LACTAMASE INHIBITORY PROTEIN TO TEM-1 BETA-LACTAMASE

Crystallization of the 1:1 molecular complex between the beta-lactamas e TEM-1 and the beta-lactamase inhibitory protein BLIP has provided an opportunity to put a stringent test on current protein-docking algori thms, Prior to the successful determination of the structure of the co mplex, nine laboratory groups were given the refined atomic coordinate s of each of the native molecules, Other than the fact that BLIP is an effective inhibitor of a number of beta-lactamase enzymes (KI for TEM -1 similar to 100 pM) no other biochemical or structural data were ava ilable to assist the practitioners in their molecular docking, In addi tion, it was not known whether the molecules underwent conformational changes upon association or whether the inhibition was competitive or non-competitive. All six of the groups that accepted the challenge cor rectly predicted the general mode of association of BLIP and TEM-1.