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Homology Modeling of Human Ccr5 and Analysis of Its Binding Properties Through Molecular Docking and Molecular Dynamics Simulation Publisher Pubmed



Shahlaei M1, 2 ; Madadkarsobhani A3, 4 ; Mahnam K5 ; Fassihi A2 ; Saghaie L2 ; Mansourian M2
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
  4. 4. Department of Life Sciences, Barcelona Supercomputing Center, 08028 Barcelona, C/Jordi Girona 31, Edificio Nexus II, Spain
  5. 5. Biology Department, Faculty of Science, Shahrekord University, Shahrekord, Iran

Source: Biochimica et Biophysica Acta - Biomembranes Published:2011


Abstract

In this study, homology modeling, molecular docking and molecular dynamics simulation were performed to explore structural features and binding mechanism of some inhibitors of chemokine receptor type 5 (CCR5), and to construct a model for designing new CCR5 inhibitors for preventing HIV attachment to the host cell. A homology modeling procedure was employed to construct a 3D model of CCR5. For this procedure, the X-ray crystal structure of bovine rhodopsin (1F88A) at 2.80 A resolution was used as template. After inserting the constructed model into a hydrated lipid bilayer, a 20 ns molecular dynamics (MD) simulation was performed on the whole system. After reaching the equilibrium, twenty-four CCR5 inhibitors were docked in the active site of the obtained model. The binding models of the investigated antagonists indicate the mechanism of binding of the studied compounds to the CCR5 obviously. Moreover, 3D pictures of inhibitor-protein complex provided precious data regarding the binding orientation of each antagonist into the active site of this protein. One additional 20 ns MD simulation was performed on the initial structure of the CCR5-ligand 21 complex, resulted from the previous docking calculations, embedded in a hydrated POPE bilayer to explore the effects of the presence of lipid bilayer in the vicinity of CCR5-ligand complex. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes © 2010 Elsevier B.V. All rights reserved.
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