School of Life Science, Chongqing University, Chongqing 401331, China.
College of Chemistry and Chemical Engineering, Chongqing University of Science and Technology, Chongqing 401331, China.
Molecules. 2018 Jun 10;23(6):1407. doi: 10.3390/molecules23061407.
In this study, quantitative structure-activity relationship (QSAR) models were determined based on 91 antioxidant tripeptides. We firstly adopted the stepwise regression (SWR) method for selecting key variables without autocorrelation and then utilized multiple linear regression (MLR), support vector machine (SVM), random forest (RF), and partial least square regression (PLS) to develop predictive QSAR models based on the screened variables. The results demonstrated that all the established models have good reliability (² > 0.86, ² > 0.70) and relatively good predictability (² > 0.88). The contribution of amino acid residues was calculated from the stepwise regression combined with multiple linear regression (SWR-MLR) method model that shows Trp, Tyr, or Cys at C-terminus is favorable for antioxidant activity of tripeptides. Nineteen antioxidant tripeptides were designed based on SWR-MLR models, and the antioxidant activity of these tripeptides were evaluated using three antioxidant assays in free radical systems (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, trolox equivalent antioxidant capacity assay, and the ferric reducing antioxidant power assay). The experimental antioxidant activities of these tripeptides were higher than the calculated/predicted activity values of the QSAR models. The QSAR models established can be used to identify and screen novel antioxidant tripeptides with high activity.
在这项研究中，基于 91 种抗氧化三肽确定了定量构效关系（QSAR）模型。我们首先采用逐步回归（SWR）方法选择无自相关的关键变量，然后利用多元线性回归（MLR）、支持向量机（SVM）、随机森林（RF）和偏最小二乘回归（PLS）基于筛选的变量开发预测性 QSAR 模型。结果表明，所有建立的模型都具有良好的可靠性（²>0.86，²>0.70）和相对较好的预测能力（²>0.88）。从逐步回归与多元线性回归（SWR-MLR）方法模型中计算氨基酸残基的贡献，表明三肽的 C 末端的色氨酸、酪氨酸或半胱氨酸有利于其抗氧化活性。基于 SWR-MLR 模型设计了 19 种抗氧化三肽，并使用自由基体系中的三种抗氧化测定法（1,1-二苯基-2-苦基肼基（DPPH）自由基清除能力、trolox 当量抗氧化能力测定法和铁还原抗氧化能力测定法）评估这些三肽的抗氧化活性。这些三肽的实验抗氧化活性高于 QSAR 模型的计算/预测活性值。所建立的 QSAR 模型可用于识别和筛选具有高活性的新型抗氧化三肽。
