Kumar Ashwani, Chauhan Shilpi
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India.
Drug Res (Stuttg). 2017 Mar;67(3):156-162. doi: 10.1055/s-0042-119725. Epub 2016 Dec 19.
Silent information regulator 2 homologue one (SIRT1) modulators have therapeutic potential for a number of diseases like cardiovascular, metabolic, inflammatory and age related disorders. Here, we have studied both activators and inhibitors of SIRT1 and constructed differential quantitative structure activity relationship (QSAR) models using CORAL software by Monte Carlo optimization method and SMILES notation. 3 splits divided into 3 subsets: sub-training, calibration and test sets, were examined and validated with a prediction set. All the described models were statistically significant models. The values of sensitivity, specificity, accuracy and Matthews' correlation coefficient for the validation set of best model were 1.0000, 0.8889, 0.9524 and 0.9058, respectively. In mechanistic interpretation, structural features important for SIRT1 activation and inhibition have been defined.
沉默信息调节因子2同源物1（SIRT1）调节剂对多种疾病具有治疗潜力，如心血管疾病、代谢疾病、炎症性疾病和与年龄相关的疾病。在此，我们研究了SIRT1的激活剂和抑制剂，并使用CORAL软件通过蒙特卡罗优化方法和SMILES符号构建了差异定量构效关系（QSAR）模型。将3次拆分分为3个子集：训练子集、校准子集和测试子集，并用一个预测集进行检验和验证。所有描述的模型都是具有统计学意义的模型。最佳模型验证集的灵敏度、特异性、准确性和马修斯相关系数值分别为1.0000、0.8889、0.9524和0.9058。在机理解释方面，已经确定了对SIRT1激活和抑制重要的结构特征。
