Virtual Screening of Penicillin-derived Inhibitors for the Metallo-β-lactamase from Bacillus cereus

Abstract

The metallo-β-lactamases (MβLs) are clinically significant enzymes which readily hydrolyze most β-lactam antibiotics. Discovering potential inhibitors for the MβLs is an expensive, time consuming endeavor. Virtual screening can sieve out inhibitor candidates with incompatible features prior to synthesis, decreasing these costs. Using Autodock 4.0, the binding locations and energies of four previously-studied potential inhibitors and four additional compounds obtained from the National Cancer Institute (NCI) database were computationally calculated. Based on the docking models of these eight compounds, we then designed several hypothetical inhibitor structures, compounds A through F, and performed their respective docking experiments. The docking results for compound F showed that it binds to the zinc containing active sites with a lowest predicted binding energy of -6.70 kcal/mol, suggesting F is the most likely potential MβL inhibitor.

Kinetic characterization of a slow-binding inhibitor of Bla2: thiomaltol

“…In this calculation, a total of 149 homologymodeled structures for Bla2 were calculated. A highresolution crystal structure (1.35 angstroms resolution) of BcII (1mqoA) was used as a template to compute the model of Bla2, and two zinc ions were inserted based on the coordination of the template structure 1mqoA 15 . To verify the homology model, PROCHECK and QMEAN program were used 16,17 .…”