دورية أكاديمية
Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies
| العنوان: | Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies |
|---|---|
| المؤلفون: | Mora Lagares, Liadys, Minovski, Nikola, Caballero Alfonso, Ana Yisel, Benfenati, Emilio, Wellens, Sara, Culot, Maxime, Gosselet, Fabien, Novič, Marjana |
| المساهمون: | Jozef Stefan International Postgraduate School Ljubljana, Slovenia, National Institute of Chemistry Llubljana (KI), Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA) |
| المصدر: | ISSN: 1661-6596. |
| بيانات النشر: | HAL CCSD MDPI |
| سنة النشر: | 2020 |
| المجموعة: | Université d'Artois: HAL |
| مصطلحات موضوعية: | P-glycoprotein, caco-2 pump out assay, molecular docking, protein homology modeling, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] |
| الوصف: | International audience ; The ABCB1 transporter also known as P-glycoprotein (P-gp) is a transmembrane protein belonging to the ATP binding cassette super-family of transporters; it is a xenobiotic efflux pump that limits intracellular drug accumulation by pumping the compounds out of cells. P-gp contributes to a decrease of toxicity and possesses broad substrate specificity. It is involved in the failure of numerous anticancer and antiviral chemotherapies due to the multidrug resistance (MDR) phenomenon, where it removes the chemotherapeutics out of the targeted cells. Understanding the details of the ligand-P-gp interaction is therefore crucial for the development of drugs that might overcome the MRD phenomenon and for obtaining a more effective prediction of the toxicity of certain compounds. In this work, an in silico modeling was performed using homology modeling and molecular docking methods with the aim of better understanding the ligand-P-gp interactions. Based on different mouse P-gp structural templates from the PDB repository, a 3D model of the human P-gp (hP-gp) was constructed by means of protein homology modeling. The homology model was then used to perform molecular docking calculations on a set of thirteen compounds, including some well-known compounds that interact with P-gp as substrates, inhibitors, or both. The sum of ranking differences (SRD) was employed for the comparison of the different scoring functions used in the docking calculations. A consensus-ranking scheme was employed for the selection of the top-ranked pose for each docked ligand. The docking results showed that a high number of π interactions, mainly π-sigma, π-alkyl, and π-π type of interactions, together with the simultaneous presence of hydrogen bond interactions contribute to the stability of the ligand-protein complex in the binding site. It was also observed that some interacting residues in hP-gp are the same when compared to those observed in a co-crystallized ligand (PBDE-100) with mouse P-gp (PDB ID: 4XWK). Our in ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03127238; https://univ-artois.hal.science/hal-03127238Test; https://univ-artois.hal.science/hal-03127238/documentTest; https://univ-artois.hal.science/hal-03127238/file/Mora%20Lagares%20et%20al.,%202020.pdfTest |
| DOI: | 10.3390/ijms21114058 |
| الإتاحة: | https://doi.org/10.3390/ijms21114058Test https://univ-artois.hal.science/hal-03127238Test https://univ-artois.hal.science/hal-03127238/documentTest https://univ-artois.hal.science/hal-03127238/file/Mora%20Lagares%20et%20al.,%202020.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.B6244196 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms21114058 |
|---|