Combining Protein Modeling and 6D-QSAR. Simulating the Binding of Structurally Diverse Ligands to the Estrogen Receptor

• Published in: Journal of medicinal chemistry Vol. 48; no. 11; pp. 3700 - 3703
• Main Authors: Vedani, Angelo, Dobler, Max, Lill, Markus A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 02.06.2005
• Subjects: Binding Sites; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Hormones. Endocrine system; Hydrogen Bonding; Ligands; Medical sciences; Models, Molecular; Pharmaceutical Preparations - chemistry; Pharmacology. Drug treatments; Quantitative Structure-Activity Relationship; Receptors, Estrogen - agonists; Receptors, Estrogen - chemistry; Toxicology; Various organic compounds; Xenobiotics - chemistry; Drug; Mimetic hormone; Estrogen receptor; Ligand; Toxicity; Chemical compound; Prediction; Molecular interaction; Endocrine disruptor; Modeling; Biological fixation; Structure activity relation; Molecular model; Multidimensional model; Binding mode; Hormonal receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm050185q

We present a concept for the in silico simulation of adverse effects triggered by drugs and chemicals. The underlying philosophy combines flexible docking (software Yeti) for the identification of the binding mode(s) and 6D-QSAR (software Quasar) for their quantification. The results obtained for 106 diverse molecules binding to the estrogen receptor (q 2 = 0.903; p 2 = 0.885) suggest that our approach is suitable for the identification of an endocrine-disrupting potential associated with drugs and chemicals.