%0 Journal Article %A Xu, Dingguo %A Zhou, Yanzi %A Xie, Daiqian %A Guo, Hua %D 2005 %T Antibiotic Binding to Monozinc CphA β-Lactamase from Aeromonas hydropila:  Quantum Mechanical/Molecular Mechanical and Density Functional Theory Studies %U https://acs.figshare.com/articles/journal_contribution/Antibiotic_Binding_to_Monozinc_CphA_Lactamase_from_i_Aeromonas_i_i_h_i_i_ydropila_i_Quantum_Mechanical_Molecular_Mechanical_and_Density_Functional_Theory_Studies/3261712 %R 10.1021/jm0505112.s001 %2 https://acs.figshare.com/ndownloader/files/5099407 %K Antibiotic Binding %K ligand %K Mechanical %K substrate %K zinc ion %K Density Functional Theory Studies %K antibiotic molecule %K quantum region %K charge density %K DFT %K CphA %K lactam %K 500 ps %K dynamics simulations %K residue %K apo enzyme %K Aeromonas hydropila %K hydrogen bond %K QM %X The active-site dynamics of apo CphA β-lactamase from Aeromonas hydropila and its complex with a β-lactam antibiotic molecule (biapenem) are simulated using a quantum mechanical/molecular mechanical (QM/MM) method and density functional theory (DFT). The quantum region in the QM/MM simulations, which includes the Zn(II) ion and its ligands, the antibiotic molecule, the catalytic water, and an active-site histidine residue, was treated using the self-consistent charge density functional tight binding (SCC-DFTB) model. Biapenem is docked at the active site unambiguously, based on a recent X-ray structure of an enzyme−intermediate complex. The substrate is found to form the fourth ligand of the zinc ion with its 3-carboxylate oxygen and to hydrogen bond with several active-site residues. The stability of the metal−ligand bonds and the hydrogen-bond network is confirmed by 500 ps molecular dynamics simulations of both the apo enzyme and the substrate−enzyme complex. The structure and dynamics of the substrate−enzyme complex provide valuable insights into the mode of catalysis in such enzymes that is central to the bacterial resistance to β-lactam antibiotics. %I ACS Publications