Molecular docking of variant of quinolone resistance-determining region in the DNA gyrase subunit A to substrates in Klebsiella pneumonia / 中华传染病杂志

ABSTRACT

Objective To investigate the binding capacities of two variants of quinolone resistance-determining region in the DNA gyrase subunit A to substrates in Klebsiella pneumonia (K.pneumonia).Methods Tertiary structures of two variants (type Ⅰ and type FH) of quinolone resistance-determining region in the DNA gyrase subunit A in K.pneumonia were predicted by homology modeling referring to that of wild type.Then,DOCK module in ArgusLab 4.1 software was used to perform molecular docking of two variants and wild type to seven kinds of quinolones substrates,and calculate binding free energies (△G).Moreover,numbers and distances of interaction between amino acid residues of DNA gyrase subunit A and ciprofloxacin were calculated.Results Molecular docking showed that binding free energies of type Ⅰ and type FH to pipemidic acid,ciprofloxacin,gatifloxacin were-26.607 50,-29.530 39,-29.493 09 kJ/mol and-26.696 44,-28.972 83,-29.590 50 kJ/mol,respectively,which declined greater than those of wild type (-27.188 82,-30.872 00 and-30.244 04 kJ/mol,respectively) and showed drug resistance.While binding free energies of type Ⅰ and type FH to levofloxacin were-29.013 81 and-29.497 57kJ/mol,respectively,and that of wild type was-28.016 20 kJ/mol.The binding free energies of type Ⅰ and type FH to nalidixic acid,norfloxacin,ofloxacin increased or declined.Moreover,if distance was less than 5 angstroms,atom pairs formed between wild type of DNA gyrase subunit A and ciprofloxacin had 16 pairs,while type Ⅰ and type FH had 2 pairs and 4 pairs,respectively.If distance was less than 4 angstroms,atom pairs formed between wild type and ciprofloxacin had 8 pairs,while type Ⅰ and type FH had no atom pairs.Conclusion Decline of binding capacities of two variants of DNA gyrase subunit A in K.pneumonia to ciprofloxacin played a role in drug resistance.