农药学学报2026，Vol.28Issue(2)：256-268,13.DOI:10.16801/j.issn.1008-7303.2026.0020
松材线虫琥珀酸脱氢酶潜在抑制剂的虚拟筛选及活性评价
Virtual screening and activity evaluation of potential inhibitors against succinate dehydrogenase from Bursaphelenchus xylophilus
摘要
Abstract
Virtual screening techniques combining homology modeling and molecular docking were employed to identify potential inhibitors of succinate dehydrogenase(SDH)from Bursaphelenchus xylophilus using the TargetMol Natural Product Database.A homology model of B.xylophilus SDH was constructed using the SWISS-MODEL server.Methodological validation of virtual screening was performed with AutoDock Vina,and the docking model exhibiting the strongest enrichment capacity for active molecules was selected and applied to screen the TargetMol Natural Product Database.Candidate compounds were prioritized based on binding energy thresholds,compliance with pesticide-likeness rules,and toxicity predictions using ProTox 3.0,followed by nematicidal activity evaluation.Interactions between candidate compounds and the target protein were analyzed using LigPlot+,PyMOL,MM/PBSA,and molecular dynamics(MD)simulations.Homology modeling results showed that two template proteins with sequence identity greater than 30%,1yq4 and 4ytp,were successfully constructed.Methodological validation indicated that the model based on 1yq4 exhibited the strongest enrichment capacity for active molecules.Using this model,four candidate compounds with favorable binding energies,pesticide-likeness,and low toxicity were identified.Nematicidal bioassays showed that after 72 h of exposure at 1.000 g/L,1,2-dimethoxy-4-propenylbenzene and glycocholic acid caused mortality rates of 98.55%and 71.52%mortality of B.xylophilus,with LC50 values of 0.066 and 0.617 g/L,respectively.Both compounds exhibited nematicidal activity,with 1,2-dimethoxy-4-propenylbenzene demonstrating particularly potent efficacy.Interaction analysis revealed that 1,2-dimethoxy-4-propenylbenzene and glycocholic acid likely inhibit BxSDH-1yq4 activity through van der Waals forces,hydrogen bonds,and hydrophobic interactions.By integrating homology modeling,virtual screening,toxicity prediction,and nematicidal activity evaluation,two natural product-derived small molecules with potent nematicidal activity against B.xylophilus were successfully identified.These findings provide a theoretical foundation for the development of highly effective and low-toxicity control agents for pine wilt disease.关键词
松材线虫/虚拟筛选/琥珀酸脱氢酶/异丁香酚甲醚/甘胺胆酸Key words
Bursaphelenchus xylophilus/virtual screening/succinate dehydrogenase/1,2-dimethoxy-4-propenylbenzene/glycocholic acid分类
信息技术与安全科学引用本文复制引用
黄夏,陈双扣,杨鑫,王瑜,朱万宏,陈秋月,陈俊杰..松材线虫琥珀酸脱氢酶潜在抑制剂的虚拟筛选及活性评价[J].农药学学报,2026,28(2):256-268,13.基金项目
重庆市科技兴林科学研究类项目(No.渝林科研YB2024-2) （No.渝林科研YB2024-2）
重庆科技大学研究生创新计划(No.YKJCX2420510). Supported by Chongqing Science and Technology for Forest Development Scientific Research Project(No.Yulin Scientific Research YB2024-2) （No.YKJCX2420510）
Chongqing University of Science and Technology Graduate Innovation Program(No.YKJCX2420510). （No.YKJCX2420510）
