Subsequently, molecular docking operations were carried out with Monte Carlo simulated annealing [45] to get the favorable binding interaction modes for NDM-1 respectively with Imipenem and Meropenem, two typical b-lactam antibiotic drugs. It was reported recently [6] that NDM-1 showed a comparatively high resistance to Imipenem and Meropenem. The binding pocket was identified using Q-SiteFinder [46] . Because binding of inhibitors in the active site may induce a conformational change to closing some flaps [47] , we adopted a flexible docking procedure to construct the binding modes of NDM-1 with Imipenem and Meropenem. Before the docking procedure, we extracted 1000 conformations of NDM-1 from the aforementioned 3-ns molecular dynamics simulation. The ligand (Imipenem or Meropenem) was then docked to all of these conformations to search for a favorable binding mode. The docking program [48] used in this study would automatically generate a diversified set of configurations by randomly changing the ligand's coordinates. When a new configuration of the ligand was generated, the search for the favorable binding was operated within a specified 3D box by the simulated annealing to optimize the purely spatial contacts as well as electrostatic interactions. Finally, the favorable binding mode thus obtained was further optimized by a short time molecular dynamics simulation (,5 ns). The binding energy was calculated using a scoring function London dG [49, 50, 51] . In all our calculations, the Merck force field (FFMM94) parameters were adopted. The most favorable binding interactions thus obtained for NDM-1 with Imipenem and Meropenem are given in Fig. 3 and Fig. 4 , respectively.