A型肉毒毒素抑制剂的分子全息定量构效关系研究  

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

作　　者：董铭心[1] 周梅 戴秋云[1] 

机构地区：[1]军事医学科学院生物工程研究所,北京100071 [2]北京宏剑讯科软件技术有限公司,北京100080

出　　处：《生物技术通讯》2007年第4期625-627,共3页Letters in Biotechnology

摘　　要：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。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 q^2=0.583 and non-cross validated coefficient square r^2= 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.

关 键 词：A型肉毒毒素 抑制剂 分子全息 定量构效关系 

分 类 号：R914.2[医药卫生—药物化学]