Theoretical Study Of Class D β-lactamase Inhibitor

Currently, β-lactam antibiotics is the most widely used and it has manyadvantages, such as strong bactericidal activity, wide range of indication, low toxicity,and clinical effect is good. However, due to the abuse ofβ-lactam antibiotics, bacteriaproduce the resistance, bacteria resistance of gram-negative bacteria towardbeta-lactam antibiotics is mainly due to the production of β-lactamases whichefficiently hydrolyze the β-lactam amide bond.In this thesis, we simulated the binding mode of complex between OXA-1andinhibitor a, b, c and d by using molecular docking and molecular dynamics. Theresults reveal that all of the four ligands have some strong hydrogen bond withOXA-1which stabilizes the complex structure. The binding free energies of these fourcomplex is-12.32kcal/mol，-15.45kcal/mol,-11.59kcal/molå'Œ-10.76kcal/mol.Additional, the residue Ser80of OXA-1has higher binding free energy with all ofthese four molecules, and Lys49has some strong interaction with molecule c and d.From these results, we consider that the inhibition of these four ligand to OXA-1is inthat order b>a>d>c. And these can be gived some theoretical support for design ofnovel inhibors of OXA-1.