Syngenta Crop Protection, Muenchwilen AG, WST-820.1.15, Schaffhauserstrasse, CH-4332 Stein, Switzerland.
J Chem Inf Model. 2010 May 24;50(5):801-14. doi: 10.1021/ci900498n.
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.
羟基苯丙酮酸双加氧酶（HPPD）已被证明是开发具有漂白性能的除草剂的非常成功的靶标，如今 HPPD 抑制剂在农用化学品市场中已得到广泛应用。先正达在 HPPD 抑制剂研究方面拥有悠久的历史，将 HPPD 选为案例研究，以验证各种基于配体和基于靶标的虚拟筛选方法，以识别具有抑制特性的化合物。二维扩展连接指纹、三维形状工具（ROCS、EON 和 Phase-shape）和药效团方法（Phase）被用作基于配体的方法；Glide 和 Gold 被用作基于靶标的方法。评估了虚拟筛选工具的虚拟筛选实用性和支架跳跃能力。特别强调了在农用化学品环境中设计虚拟筛选活动时需要考虑的具体陷阱，与制药环境相比。
