3D QSAR studies of dioxins and dioxin-like compounds using CoMFA and CoMSIA
3D QSAR studies of dioxins and dioxin-like compounds using CoMFA and CoMSIA
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DOI：
10.1016/j.chemosphere.2006.01.010
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发表时间：
2006-10-01
期刊：
影响因子：
8.8
通讯作者：
Cho, Seung Joo
中科院分区：
文献类型：
--
作者：
Ashek, Ali;Lee, Cheolju;Cho, Seung Joo
在本研究中，我们对芳香烃（二噁英）受体的结构多样的配体进行了比较分子力场分析（CoMFA）和比较分子相似性指数分析（CoMSIA），以探究结合的物理化学要求。所有的CoMFA和CoMSIA模型都给出了q²值大于0.5以及r²值大于0.84。这些模型的预测能力通过一个外部测试集得到了验证，该测试集给出了令人满意的预测r²值。通过组合修正训练集的CoMFA模型获得了最佳预测结果（q² = 0.631，r² = 0.900），对于测试化合物给出的预测残差值为0.02 log单位。CoMSIA研究的加入阐明了疏水性和氢键的作用，以及CoMFA所揭示的空间和静电性质的影响。我们提出了一个由四种结构不同的化合物组成的模型，它对各种配体具有良好的预测能力。我们的定量构效关系（QSAR）模型与之前所有建立的配体结构多样性较低的QSAR模型是一致的。（c）2006爱思唯尔有限公司。保留所有权利。
In the present study we have performed comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) on structurally diverse ligands of Ah (dioxin) receptor to explore the physico-chemical requirements for binding. All CoMFA and CoMSIA models have given q(2) value of more than 0.5 and r(2) value of more than 0.84. The predictive ability of the models was validated by an external test set, which gave satisfactory predictive r2 values. Best predictions were obtained with CoMFA model of combined modified training set (q(2) = 0.63 1, r(2) = 0.900), giving predictive residual value = 0.02 log unit for the test compound. Addition of CoMSIA study has elucidated the role of hydrophobicity and hydrogen bonding along with the effect of steric and electrostatic properties revealed by CoMFA. We have suggested a model comprises of four structurally different compounds, which offers a good predictability for various ligands. Our QSAR model is consistent with all previously established QSAR models with less structurally diverse ligands. (c) 2006 Elsevier Ltd. All rights reserved.