通过集成虚拟筛选方法发现潜在的乙酰羟基酸合酶共价抑制剂
Discovery of Potential Acetohydroxyacid Synthase Covalent Inhibitors with Integrated Virtual Screening Approach.
摘要(中文译文)
乙酰羟酸合成酶（AHAS）是50多种商业化除草剂的重要靶标。然而，杂草中日益严重的除草剂抗性使防治变得困难，开发共价抑制剂可能是一种有效策略。本研究基于共价结合效应，构建了一种结合基于结构、基于配体和分子模拟计算的混合虚拟筛选策略，并首次将其用于发现潜在的AHAS共价抑制剂。通过农药相似性筛选获得了包含5178个小分子磺酰氟化合物的精炼数据库。该数据库首先通过非共价对接进行初步筛选，评分较高的化合物再利用整合的二维和三维相似性搜索工具进行重新排序，获得723个分子。通过共价对接和DFT计算，成功筛选出两个潜在的共价抑制剂。值得注意的是，其中一个对AHAS表现出优异的抑制活性，其值为0.12 μM，优于双草醚（0.44 μM）。本研究为开发共价抑制剂农药提供了一个有意义的起点。
Abstract
Acetohydroxyacid synthase (AHAS) is an important target for over 50 commercial herbicides. However, increasing herbicide resistance in weeds has made control difficult, and developing covalent inhibitors may be an effective strategy. Here, a hybrid virtual screening strategy combining structure-based, ligand-based, and molecular simulation calculations was developed based on covalent binding effects and first employed to discover potential AHAS covalent inhibitors. A refined database of 5178 sulfonyl fluoride-containing small molecules was obtained via pesticide similarity screening. The database was initially screened by noncovalent docking, and higher-scoring compounds were reranked using integrated 2D and 3D similarity search tools to obtain 723 molecules. Two potential covalent inhibitors, and , were successfully screened by covalent docking and DFT calculations. Notably, showed excellent inhibitory activity against AHAS with a value of 0.12 μM, superior to bispyribac (0.44 μM). This work offers a meaningful starting point for developing covalent inhibitor pesticides.
如何引用
AMA
Fangping Zhong, Wei Zhang, Yan Li, Chao Chen, Xiuhai Gan. Discovery of Potential Acetohydroxyacid Synthase Covalent Inhibitors with Integrated Virtual Screening Approach.. Journal of agricultural and food chemistry. 2026; doi:10.1021/acs.jafc.5c11707.
APA
Fangping Zhong, Wei Zhang, Yan Li, Chao Chen, Xiuhai Gan (2026). Discovery of Potential Acetohydroxyacid Synthase Covalent Inhibitors with Integrated Virtual Screening Approach.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.5c11707
GB/T 7714
Fangping Zhong, Wei Zhang, Yan Li, Chao Chen, Xiuhai Gan. Discovery of Potential Acetohydroxyacid Synthase Covalent Inhibitors with Integrated Virtual Screening Approach.[J]. Journal of agricultural and food chemistry, 2026 doi:10.1021/acs.jafc.5c11707.
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