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Molecular modeling study of the differential ligand–receptor interaction at the μ, δ and κ opioid receptors

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Abstract

3D models of the opioid receptors μ, δ and κ were constructed using BUNDLE, an in-house program to build de novo models of G-protein coupled receptors at the atomic level. Once the three opioid receptors were constructed and before any energy refinement, models were assessed for their compatibility with the results available from point-site mutations carried out on these receptors. In a subsequent step, three selective antagonists to each of three receptors (naltrindole, naltrexone and nor-binaltorphamine) were docked onto each of the three receptors and subsequently energy minimized. The nine resulting complexes were checked for their ability to explain known results of structure-activity studies. Once the models were validated, analysis of the distances between different residues of the receptors and the ligands were computed. This analysis permitted us to identify key residues tentatively involved in direct interaction with the ligand.

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Authors and Affiliations

  1. Centro di Ricerca Interdipartimentale di Scienze Computazionali e Biotecnologiche (CRISCEB), Seconda Universitá degli Studi di Napoli, Via Costantinopoli 16, I-80138, Naples, Italy

    Marta Filizola & Maria Carteni-Farina

  2. Dept. d'Enginyeria Quimica, UPC, ETS d'Enginyers Industrials, Av, Diagonal 647, E-08028, Barcelona, Spain

    Juan J. Perez

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  1. Marta Filizola
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  2. Maria Carteni-Farina
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  3. Juan J. Perez
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Filizola, M., Carteni-Farina, M. & Perez, J.J. Molecular modeling study of the differential ligand–receptor interaction at the μ, δ and κ opioid receptors. J Comput Aided Mol Des 13, 397–407 (1999). https://doi.org/10.1023/A:1008079823736

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