3D QSAR studies of dioxins and dioxin-like compounds using CoMFA and CoMSIA.
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.
Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, South Korea.
Ali
A
Ashek
Cheolju
C
Lee
Hyunsung
H
Park
Seung Joo
SJ
Cho
D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology; D000072338:Dibenzofurans, Polychlorinated; D016018:Least-Squares Analysis; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D008024:Ligands; D009281:Naphthalenes; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon