Multiple Binding Modes in 3D-QSAR: Microbial Degradation of Polychlorinated Biphenyls

Abstract

The published microbial degradation rates of nineteen polychlorinated biphenyls (PCB) were correlated with their structure and properties. A Free-Wilson-like calculation of the de novo binding energy contributions of the chlorine substituents was applied, considering simultaneous realization of up to four binding modes for each congener. Influence of the PCB concentration in the vicinity of the degrading enzyme on the degradation rate was taken into account assuming pseudo-equilibrium PCB distribution in the microbial biomass. The resulting map of the binding site has two attractive regions and two repulsive regions positioned in the way that the PCB congeners bind to them in a non-planar conformation. The results are consistent with two commonly accepted perceptions of PCB degradation: (1) for majority of the studied congeners, the attack starts in non-chlorinated 2,3-position or equivalent position; (2) the less chlorinated phenyl ring is usually degraded first.