Volume 9, Issue 1 (2018)
JMBS 2018, 9(1): 47-52 |
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Taghdir M, Dehghan Banadaki N. Probable Binding Sites of Mesd and Its Peptide Derived from Carboxyl Terminal on LRP6 First and Second Beta-Propeller Domains; A Structural Approach in Drug Design. JMBS 2018; 9 (1) :47-52
URL: http://biot.modares.ac.ir/article-22-15570-en.html
URL: http://biot.modares.ac.ir/article-22-15570-en.html
1- Biophysics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran, Biophysics Department, Biological Sciences Faculty, Tarbiat Modares University, Nasr Bridge, Jalal-Al-Ahmad Highway, Tehran, Iran , taghdir@modares.ac.ir
2- Biophysics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran
2- Biophysics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran
Abstract: (7645 Views)
Aims: The Mesd is a universal inhibitor and has therapeutic effect against triple negative breast cancer. The peptide derived from carboxyl terminal, similar to protein, acts as an inhibitor of the pathway. The aim of this study was to investigate the probable binding sites of Mesd and its peptide derived from carboxyl terminal on LRP6 first and second beta-propeller domains from a structural point of view in drug design.
Materials & Methods: This experimental study was conducted, using blind and site-directed molecular docking simulation with ClusPro and Haddock and molecular dynamic simulation. The binding sites of Mesd and the peptide on the first and second beta-propeller domains of receptor LRP6 were investigated and the selected complexes were structurally analyzed.
Findings: Extensive levels of Mesd protein were found to interact with LRP6 and the levels involved in the peptide were much lower. The binding region of Mesd to LRP6 was from the carboxyl terminal. The binding region of the peptide and the protein on LRP6 was a similar region between First and Second Beta-Propeller Domains of LRP6. The RMSD and RMSF chart of the Mesd complex and its peptide was approximately the same with the first functional domain of the LRP6 co-receptor.
Conclusion: The binding region of the peptide and the protein on LRP6 is not completely similar, but according to molecular simulation of selected complexes, the pattern of the inhibition mechanism is common and emphasizes on inter domain motion control from a structural point of view. Interactive region of each ligand is similar to a region of the co-receptor, which has maximum flexibility. Molecular docking simulation of Mesd and co-receptor shows important role of carboxyl terminal of the protein to bind to LRP6.
Materials & Methods: This experimental study was conducted, using blind and site-directed molecular docking simulation with ClusPro and Haddock and molecular dynamic simulation. The binding sites of Mesd and the peptide on the first and second beta-propeller domains of receptor LRP6 were investigated and the selected complexes were structurally analyzed.
Findings: Extensive levels of Mesd protein were found to interact with LRP6 and the levels involved in the peptide were much lower. The binding region of Mesd to LRP6 was from the carboxyl terminal. The binding region of the peptide and the protein on LRP6 was a similar region between First and Second Beta-Propeller Domains of LRP6. The RMSD and RMSF chart of the Mesd complex and its peptide was approximately the same with the first functional domain of the LRP6 co-receptor.
Conclusion: The binding region of the peptide and the protein on LRP6 is not completely similar, but according to molecular simulation of selected complexes, the pattern of the inhibition mechanism is common and emphasizes on inter domain motion control from a structural point of view. Interactive region of each ligand is similar to a region of the co-receptor, which has maximum flexibility. Molecular docking simulation of Mesd and co-receptor shows important role of carboxyl terminal of the protein to bind to LRP6.
Article Type: Research Paper |
Subject:
Agricultural Biotechnology
Received: 2016/03/8 | Accepted: 2018/01/27 | Published: 2018/05/22
Received: 2016/03/8 | Accepted: 2018/01/27 | Published: 2018/05/22
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