基于随机森林的TRPV1通道与调节剂的分子对接重打分模型构建  

Construction of a Rescoring Model for Molecular Docking of TRPV1 and Its Regulators Based on Random Forest Algorithm

作　　者：郭怡萱 杨芷江 黄腾鑫 王云帆 潘里 王亮亮 丁俊杰 GUO Yixuan;YANG Zhijiang;HUANG Tengxin;WANG Yunfan;PAN Li;WANG Liangliang;DING Junjie(State Key Laboratory of NBC Protection for Civilian,Beijing 102205,China;Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]国民核生化灾害防护国家重点实验室,北京102205 [2]河北医科大学,河北石家庄050011

出　　处：《防化研究》2024年第5期70-76,共7页CBRN DEFENSE

摘　　要：本研究旨在利用随机森林算法开发一种针对瞬时受体电位香草酸-1(Transient Receptor Potential Vanilloid-1,TRPV1)通道特异性分子对接的重打分模型TRPV1-Rescore,以寻找潜在的TRPV1调节剂。依托ChEMBL数据库检索与TocoDDB网站生成,获得2909个TRPV1通道调节剂和3000个诱饵化合物分别作为建模的正、负数据集,将其与TRPV1通道进行分子对接,得到对接打分和活性位点关键残基结合能等作为特征参数,应用随机森林算法,构建了TRPV1通道与调节剂分子对接重打分模型TRPV1-Rescore,采用内部五折交叉验证对模型进行了评估。结果表明,外部测试集验证显示该模型的准确率、精确度和召回率分别为0.924、0.916、0.923,证明TRPV1-Rescore模型性能稳健,可用于TRPV1调节剂的虚拟筛选,此模型提升了预测TRPV1通道与其调节剂结合能力的准确性。本研究为新型TRPV1调节剂的设计和发现提供了新方法和新手段。This study aimed to develop a specific molecular docking rescoring model,which was referred as TRPV1 Rescore,for the Transient Receptor Potential Vanilloid-1(TRPV1)channel by Random Forest algorithm to identify potential TRPV1 modulators.Based on ChEMBL database retrieval and TocoDDB website generation,2909 TRPV1 channel modulators and 3000 decoy compounds were obtained as positive and negative data sets for modeling,and molecular docking was performed between the data sets and TRPV1 channels.Characteristic parameters such as docking score and binding energy of key residues at the active site were obtained,and the Random Forest algorithm was applied to construct a rescoring model for the docking of TRPV1 channel and regulator molecules,TRPV1-Rescore.The model was evaluated by internal five-fold crossvalidation and the results showed that the accuracy,precision and recall rate of the model are 0.924,0.916 and 0.923,respectively,which proved that the TRPV1-Rescore model was robust and could be used for virtual screening of TRPV1 regulators.This model improved the accuracy of predicting the binding ability of TRPV1 channels to their regulators.This study provides a new method and means for the design and discovery of new TRPV1 regulators.

关 键 词：TRPV1通道 调节剂 随机森林 分子对接 打分函数 

分 类 号：R914[医药卫生—药物化学]