HPPD: ligand- and target-based virtual screening on a herbicide target.
Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment.
López-Ramos
Miriam
M
Syngenta Crop Protection, Muenchwilen AG, WST-820.1.15, Schaffhauserstrasse, CH-4332 Stein, Switzerland. miriam.lopez-ramos@m4x.org
Perruccio
Francesca
F
D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006540:Herbicides / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010944:Plants / Q000201:enzymology*
D006540:Herbicides; D008024:Ligands; D015111:4-Hydroxyphenylpyruvate Dioxygenase