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LigPath: a module for predictive calculation of a ligand’s pathway into a receptor-application to the gpH1 - receptor

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Abstract

Until now, the access of ligands into the binding pocket of a G-protein coupled receptor has scarcely been studied using molecular-modeling techniques because of the lack of sufficient algorithms. Neither with Monte-Carlo- nor with Molecular Dynamics Simulations can the penetration of a ligand into the binding pocket of a receptor be calculated because of the excessive amount of computing time needed. Therefore, a new algorithm LigPath for approximate calculation of a ligand’s pathway into the binding pocket has been developed. This new algorithm is based on a linkage of directional guiding of the ligand, Monte-Carlo-Search and minimization. In order to evaluate the performance of the algorithm, the guinea-pig histamine H1 receptor was investigated in combination with one of its potent agonists, histaprodifen, which is proposed to bind in a pocket deep between the transmembrane helices of the receptor. Our calculations show that the amino acids Tyr194, Phe193, Phe436 and Phe433 guide the positively charged histaprodifen from the extracellular part of the receptor into the binding pocket.

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Authors and Affiliations

  1. Department of Pharmaceutical and Medicinal Chemistry, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany

    Andrea Straßer

  2. EDV-Referent, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany

    Hans-Joachim Wittmann

Authors
  1. Andrea Straßer
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  2. Hans-Joachim Wittmann
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Correspondence to Andrea Straßer.

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Straßer, A., Wittmann, HJ. LigPath: a module for predictive calculation of a ligand’s pathway into a receptor-application to the gpH1 - receptor. J Mol Model 13, 209–218 (2007). https://doi.org/10.1007/s00894-006-0152-9

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  • DOI: https://doi.org/10.1007/s00894-006-0152-9

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