Predictions of Binding for Dopamine D2 Receptor Antagonists by the SIE Method

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• 作者：Yeng-Tseng Wang ; Zhi-Yuan Su ; Chang-Huain Hsieh ; Cheng-Lung Chen
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2009
• 出版时间：October 26, 2009
• 年：2009
• 卷：49
• 期：10
• 页码：2369-2375
• 全文大小：390K
• 年卷期：v.49,no.10(October 26, 2009)
• ISSN：1549-960X

文摘

The control of tetralindiol derivative antagonists released through the inhibition of dopamine D2 receptors has been identified as a potential target for the treatment of schizophrenia. We employed molecular dynamics simulation techniques to identify the predicted D2 receptor structure. Homology models of the protein were developed on the basis of crystal structures of four receptor crystals. Compound docking revealed the possible binding mode. In addition, the docking analyses results indicate that five residues (Asp72, Val73, Cys76, Leu183, and Phe187) were responsible for the selectivity of the tetralindiol derivatives. Our molecular dynamics simulations were applied in combination with the solvated interaction energies (SIE) technique to predict the compounds’ docking modes in the binding pocket of the D2 receptor. The simulations revealed satisfactory correlations between the calculated and experimental binding affinities of all seven tetralindiol derivative antagonists, as indicated by the obtained R² value of 0.815.