Molecular dynamics simulations of acylpeptide hydrolase bound to chlorpyrifosmethyl oxon and dichlorvos

International Journal of Molecular Sciences
Hanyong JinWeiwei Han

Abstract

Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well as the different OP compounds binding and inducing conformational changes in two domains, namely, α/β hydrolase and β-propeller, remain poorly understood. We report a computational study of APH bound to chlorpyrifosmethyl oxon and dichlorvos. In our docking study, Val471 and Gly368 are important residues for chlorpyrifosmethyl oxon and dichlorvos binding. Molecular dynamics simulations were also performed to explore the conformational changes between the chlorpyrifosmethyl oxon and dichlorvos bound to APH, which indicated that the structural feature of chlorpyrifosmethyl oxon binding in APH permitted partial opening of the β-propeller fold and allowed the chlorpyrifosmethyl oxon to easily enter the catalytic site. These results may facilitate the design of APH-targeting drugs with improved efficacy.

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Citations

Apr 5, 2020·International Journal of Molecular Sciences·Jingxuan ZhuWeiwei Han
Sep 20, 2019·Physical Chemistry Chemical Physics : PCCP·Ruihan Wang, Dingguo Xu

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Methods Mentioned

BETA
PCA

Software Mentioned

CDOCKER
Discovery Studio
Gaussian view
Systat
Gaussian
AutoDockVina
GROMACS
AutoDock Vina
CHARMM
Multiwfn

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