Antibiotic binding to dizinc beta-lactamase L1 from Stenotrophomonas maltophilia: SCC-DFTB/CHARMM and DFT studies.

A dizinc beta-lactamase (L1 from Stenotrophomonas maltophilia) complexed with an antibiotic compound (moxalactam) has been studied using a hybrid quantum mechanical/molecular mechanical (QM/MM) approach. The QM region is described by the self-consistent charge-density functional tight binding (SCC-DFTB) model while the MM by CHARMM. The Michaelis complex, which is constructed from a recent X-ray structure of the L1 enzyme with the hydrolyzed moxalactam, is simulated by molecular dynamics. The simulation yields valuable insights into substrate-enzyme interaction, whose implications in the enzyme catalysis are discussed. Finally, the QM/MM results are compared with a high-level density functional theory study of a truncated active-site model and the agreement provides strong support for the SCC-DFTB treatment of the QM region.