摘要
目的世界范围内斜蛛属蜘蛛咬伤事故不断增多,急需探索天然抑制剂来抑制最显著的鞘磷脂酶D和透明质酸酶。方法通过DrugRep服务器使用中药抗鞘磷脂酶D(PDB ID:2F9R)和透明质酸酶进行虚拟筛选。通过同一服务器预测吸收、分布、代谢和排泄(ADME)参数。此外,使用CABS-flex 2.0工具进行分子动力学模拟,确定潜在最佳天然抑制剂的优先次序。结果从分子对接和ADME参数来看,中药抑制抗鞘磷脂酶D和透明质酸酶的天然抑制剂中,Tiliroside和Digitoxin表现最佳。而洋地黄毒苷和β-胡萝卜素是对透明质酸酶最有效的抑制剂。分子动力学模拟证明了对接复合物的稳定性。结论通过中药对斜蛛属蜘蛛毒液酶的计算机模拟抑制得到证明,值得开展湿实验分析。
Objective Loxosceles spider bite accidents are rising in wide areas of the world which necessitates the exploration of natural inhibitors to inhibit the most significant enzymes,namely sphingomyelinase D(Smase D)and hyaluronidase.Methods Virtual screening using traditional Chinese medicine(TCM)against Smase D(PDB ID:2F9R)and hyaluronidase was performed by the DrugRep server.Absorption,distribution,metabolism,and excretion(ADME)parameters were predicted via the same server.In addition,molecular dynamics(MD)simulation was conducted using CABS-flex 2.0 tool to prioritize the best potential natural inhibitors.Results Tiliroside and Digitoxin were the best natural inhibitors from TCM to Smase D and hyaluronidase in terms of molecular docking and ADME parameters,while Digitoxin andβ-carotene were the most potent inhibitors against hyaluronidase.MD simulations demonstrated the stability of the docked complexes.Conclusion In-silico inhibition of Loxosceles spidervenom enzymes through TCM was demonstrated,which deserves wet-lab experimentation.
关键词
斜蛛属蜘蛛
鞘磷脂酶D
中医药
分子对接
分子动力学模拟
吸收、分布、代谢与排泄(ADME)
Loxosceles spider
Sphingomyelinase D(Smase D)
Traditional Chinese medicine(TCM)
Molecular docking
Molecular dynamics(MD)simulations
Absorption,distribution,metabolism
and excretion(ADME)
