Ashek Ali, Lee Cheolju, Park Hyunsung, Cho Seung Joo
Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, South Korea.
Chemosphere. 2006 Oct;65(3):521-9. doi: 10.1016/j.chemosphere.2006.01.010. Epub 2006 Feb 17.
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 r(2) values. Best predictions were obtained with CoMFA model of combined modified training set (q(2) = 0.631, 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.
在本研究中，我们对芳烃（二噁英）受体结构多样的配体进行了比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA），以探索结合所需的物理化学条件。所有CoMFA和CoMSIA模型的q(2)值均大于0.5，r(2)值均大于0.84。模型的预测能力通过外部测试集进行了验证，该测试集给出了令人满意的预测r(2)值。使用组合修改训练集的CoMFA模型获得了最佳预测结果（q(2)=0.631，r(2)=0.900），测试化合物的预测残差值为0.02对数单位。CoMSIA研究的补充阐明了疏水性和氢键的作用，以及CoMFA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，该模型对各种配体具有良好的预测能力。我们建立的定量构效关系（QSAR）模型与所有先前建立的针对结构多样性较低的配体的QSAR模型一致。
