New　Delhi　metallo-β-lactmase-1　(NDM-1)　is　an　enzyme　that　confers　antibiotic　resistance　to　bacteria　and　is　thus　a　serious　threat　to　human　health.　Almost　all　clinically　available　β-lactam　antibiotics　can　be　hydrolyzed　by　NDM-1.　To　determine　the　mechanism　behind　the　wide　substrate　diversity　and　strong　catalytic　ability　of　NDM-1,　we　explored　the　molecular　interactions　between　NDM-1　and　different　β-lactam　antibiotics　using　computational　methods.　Molecular　dynamics　simulations　and　binding　free　energy　calculations　were　performed　on　enzyme-substrate　(ES)　complex　models　of　NDM-1-Meropenem,　NDM-1-Nitrocefin,　and　NDM-1-Ampicillin　constructed　by　molecular　docking.　Our　computational　results　suggest　that　mutant　residues　Ile35　and　Lys216,　and　active　site　loop　L1　residues　65-73　in　NDM-1　play　crucial　roles　in　substrate　recognition　and　binding.　The　results　of　our　study　provide　new　insights　into　the　mechanism　behind　the　enhanced　substrate　binding　and　wider　substrate　spectrum　of　NDM-1　compared　with　its　homologous　enzymes　CcrA　and　IMP-1.　These　insights　may　be　useful　in　the　discovery　and　design　of　specific　and　potent　inhibitors　against　NDM-1.　©　2013　Elsevier　Inc.