Discovery of novel HPPD inhibitors: Virtual screening, molecular design, structure modification and biological evaluation

Integrated Virtual Screening and Validation toward Potential HPPD Inhibition Herbicide

“…The HPPD crystal complex 7X5U, downloaded from the Protein Data Bank (PDB, ), was selected to build CBP models with Discovery Studio software (DS, BIOVIA Inc. San Diego, CA, 2019), and these models were evaluated by 15 active and 128 inactive molecules. , Initially, 7X5U was subjected to the “Prepare Protein” procedure, followed by cutting the ligand (9R6502) for backup. Then, CBP models were generated and validated through the “Receptor-Ligand Pharmacophore Generation” module, and all parameters were left as default …”

“…Computer-aided drug design/discovery (CADD) has become a crucial part of drug development, and the combination of pharmacophore model screening and molecular docking has been widely adopted. − Pharmacophore models are commonly generated based on a series of ligand characteristics, receptor structure, and CBP, which have been extensively applied alone or in combination in the discovery of HPPD inhibitors. − Subsequently, molecular docking was carried out to validate the specific binding patterns between the ligands and HPPD, as well as ensure a relatively high binding energy. ,− However, a drawback in the molecular docking process still exists, in which it is hard to distinguish the optimal conformation. − A novel consensus docking approach has been reported recently in the discovery of HPPD inhibitors, which compensated for this shortcoming and improved the accuracy and reliability of the docking process …”

Novel Inhibitor of Glutamate-Cysteine Ligase Catalytic Subunit against Tribolium castaneum: High-Throughout Virtual Screening, Molecular Docking and Dynamics Simulation, and Bioassay

“…Structure-Based Pharmacophore (SBP) was generated using the Discovery Studio CATALYST SBP module . SBP directly obtains the interaction site map from the characteristics of the receptor site using the protein active sites and, based on this information, is used to screen the 3D database.…”

“…Structure-Based Pharmacophore (SBP) was generated using the Discovery Studio CATALYST SBP module. 27 SBP directly obtains the interaction site map from the characteristics of the receptor site using the protein active sites and, based on this information, is used to screen the 3D database. First, in the binding sphere including the active residues, the interaction map was generated using the Pharmacophore | Edit and Cluster Pharmacophore Features (Figure S4).…”

4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Molecular Design to Synthesis

“…Leng et al utilized HipHop and CBP pharmacophore models for screening 1 000 000 molecules containing diketone subunit from PubChem database. 58 Subsequently, 1591 compounds exhibiting favorable fit values were selected and further filtered through molecular docking and ADMET prediction. Combining the structure of screening molecules, compounds S33 to S35 were successfully designed (SI, Scheme S12).…”