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Tetrahydroisoquinolines acting as dopaminergic ligands. A molecular modeling study using MD simulations and QM calculations

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Abstract

A molecular modeling study on 16 1-benzyl tetrahydroisoquinolines (BTHIQs) acting as dopaminergic ligands was carried out. By combining molecular dynamics simulations with ab initio and density functional theory (DFT) calculations, a simple and generally applicable procedure to evaluate the binding energies of BTHIQs interacting with the human dopamine D2 receptor (D2 DR) is reported here, providing a clear picture of the binding interactions of BTHIQs from both structural and energetic viewpoints. Molecular aspects of the binding interactions between BTHIQs and the D2 DR are discussed in detail. A significant correlation between binding energies obtained from DFT calculations and experimental pKi values was obtained, predicting the potential dopaminergic effect of non-synthesized BTHIQs.

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Acknowledgments

Grants from Universidad Nacional de San Luis (UNSL) partially supported this work. This research was also supported by the Spanish “Ministerio de Educación y Ciencia” grant SAF 2007–63142. S.A.A. thanks a postdoctoral fellowship of CONICET-Argentina. R.D.E. is a member of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-Argentina) staff.

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Authors and Affiliations

  1. Departamento de Química, Universidad Nacional de San Luis, San Luis, Argentina

    Sebastián Andujar, Fernando Suvire & Ricardo D. Enriz

  2. IMIBIO-SL (CONICET), Chacabuco 915, 5700, San Luis, Argentina

    Sebastián Andujar & Ricardo D. Enriz

  3. Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, 46100, Burjassot, Valencia, Spain

    Inmaculada Berenguer, Nuria Cabedo, Paloma Marín, Laura Moreno, María Dolores Ivorra & Diego Cortes

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  1. Sebastián Andujar
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  2. Fernando Suvire
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Correspondence to Ricardo D. Enriz.

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Andujar, S., Suvire, F., Berenguer, I. et al. Tetrahydroisoquinolines acting as dopaminergic ligands. A molecular modeling study using MD simulations and QM calculations. J Mol Model 18, 419–431 (2012). https://doi.org/10.1007/s00894-011-1061-0

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