Strasser, Andrea and Wittmann, Hans-Joachim (2007) LigPath: a module for predictive calculation of a ligand's pathway into a receptor-application to the gpH(1)-receptor. JOURNAL OF MOLECULAR MODELING, 13 (1). pp. 209-218. ISSN 1610-2940,
Full text not available from this repository. (Request a copy)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 H-1 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-COUPLED RECEPTORS; CANNABINOID CB1 RECEPTOR; MOLECULAR-DYNAMICS; HISTAMINE H-1-RECEPTOR; AGONIST; BINDING; RHODOPSIN; MECHANISM; ACTIVATION; DOMAIN; guinea-pig histamine H-1 receptor; G-protein-coupled receptor; histaprodifen; molecular modeling; pathway |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jan 2021 10:16 |
| Last Modified: | 12 Jan 2021 10:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33454 |
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