Molecular dynamics simulations of the detoxification of paraoxon catalyzed by phosphotriesterase.

ABSTRACT: Combined QM(PM3)/MM molecular dynamics simulations together with QM(DFT)/MM optimizations for key configurations have been performed to elucidate the enzymatic catalysis mechanism on the detoxification of paraoxon by phosphotriesterase (PTE). In the simulations, the PM3 parameters for the phosphorous atom were reoptimized. The equilibrated configuration of the enzyme/substrate complex showed that paraoxon can strongly bind to the more solvent-exposed metal ion Zn(beta), but the free energy profile along the binding path demonstrated that the binding is thermodynamically unfavorable. This explains why the crystal structures of PTE with substrate analogues often exhibit long distances between the phosphoral oxygen and Zn(beta). The subsequent SN2 reaction plays the key role in the whole proc

SUBMITTER: Zhang X 

PROVIDER: S-EPMC2754597 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature