A型肉毒毒素抑制剂的分子全息定量构效关系研究

目的:建立A型肉毒毒素抑制剂的定量构效关系模型。方法:应用分子全息定量构效关系(HQSAR)技术,研究了14种A型肉毒毒素抑制剂的抑制活性与其二维分子结构之间的关系,讨论了碎片区分参数及碎片长度对模型质量的影响。结果:最佳全息条件下产生的模型相关系数r2为0.780,交叉验证相关系数q2LOO为0.583。所建模型具有良好的拟和效果和较高的预测能力,HQSAR模型贡献图显示抑制剂分子中的噻吩环及羟胺对活性有较大贡献。结论:本研究对新抑制剂的设计具有一定的指导作用。

Hologram Quantitative Structure-Activity Relationship Study of Botulinum Neurotoxin A Inhibitors

Objective:To establish quantitative structure-activity relationship model of botulinum neurotoxin A inhibitors.Methods:Hologram quantitative structure-activity relationship(HQSAR)was used to investigate the relationships of inhibitory activity of 14 botulinum neurotoxin A inhibitors with their structure.The parameters of molecular fragment size,fragment substructural type and molecular hologram length were selected in the HQSAR models.Results:The best HQSAR model was statistically significant with the LOO coefficient square q2=0.583 and non-cross validated coefficient square r2=0.780.Established model has a good fitting effect and highly predictive ability,the contribution maps obtained from these models indicate that thiophene and hydroxylamine have important contributions to activity.Conclusion:This study may provide a useful guideline for the design of novel inhibitor.