摘要
从20种天然氨基酸的41个randic molecular profiles非零描述符、44个eigenvalue based indices非零描述符和47个walk and path counts非零描述符分别进行主成分分析,得出一种新的氨基酸描述符-SVREW。将其应用于血管紧张素转化酶(ACE)抑制二肽和ACE抑制三肽、苦味二肽和苦味四肽、后叶催产素类似物、HLA-A*0201限制性CTL表位肽的结构表征,应用多元线性回归(MLR)建立定量构效关系模型,同时采用内部与外部双重验证的方法验证模型的稳定性。所建ACE抑制二肽、ACE抑制三肽、苦味二肽、苦味四肽、后叶催产素类似物、HLA-A*0201限制性CTL表位肽的模型复相关系数(R2cum)分别为0.994,0.797,0.948,0.878,0.686,0.720;留一法交互校验复相关系数(R2cv)分别为0.955,0.859,0.879,0.958,0.796,0.843;外部样本校验相关系数(Q2ext)分别为0.990,0.954,0.890,0.950,0.748,0.773。经研究表明SVREW描述符用于肽分子结构表征所建模型的稳定性与预测能力均较好,有望成为多肽定量构效关系研究中一种有效的结构表征方法,可对新药物的发现和研究提供指导。
A new descriptor of amino acids,SVREW,was derived from principal components analysis of 41 randic molecular profiles descriptors,44 eigenvalue-based indices descriptors and the matrix of 47 walk and path counts descriptors of amino acids. The structures of angiotensin-converting enzyme（ACE） inhibiting dipeptides and tripeptides,bitter tasting thresholds dipeptides and tetrapeptides,oxytocin,HLA-A＊0201 restricted CTL epitope were characterized with SVREW,using multiple linear regression（MLR） to establish a quantitative structure-activity relationship,at the same time,adopting the methods of internal and external for dual verification of the stability of the model.The relevant statistical parameters were as follows： the correlation coefficient（R^2cum）,leava-one-out（LOO） cross-validation correlation coefficient（R^2cv） and external validation correlation coefficient（Q^2ext） were 0. 994,0. 797,0. 948 for ACE inhibition dipeptides model; 0. 896,0. 686,0. 720 for ACE inhibition tripeptides models, 0. 955, 0. 859, 0. 879 for BTT dipeptides model, 0. 958,0. 796,0. 843 for BTT tetrapeptides model,0. 990,0. 954,0. 890 for oxytocin model,0. 950,0. 748,0. 773 for HLA-A^＊0201 restricted CTL epitope model,respectively. Studies showed that the MLR models constructed by SVREW descriptor had good fitting and predictive abilities,which was an effective structure characterization method in peptide drugs QSAR study and provided a guidance for new drug discovery and research.
出处
《分析测试学报》
CAS
CSCD
北大核心
2017年第2期224-229,235,共7页
Journal of Instrumental Analysis
基金
国家自然科学基金(21475081)
陕西省自然科学基础研究计划(2015JM2057)
陕西科技大学研究生创新基金
关键词
定量构效关系
氨基酸描述符
多元线性回归
肽
quantitative structure-activity relationship
amino acid descriptor
multiple linear regression
peptides
