title: Homology modeling of human CCR5 and analysis of its binding properties through molecular docking and molecular dynamics simulation.
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 2.80Å resolution was used as template. After inserting the constructed model into a hydrated lipid bilayer, a 20ns 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Shahlaei
authors.forename: Armin
authors.initials: A
authors.lastname: Madadkar-Sobhani
authors.forename: Karim
authors.initials: K
authors.lastname: Mahnam
authors.forename: Afshin
authors.initials: A
authors.lastname: Fassihi
authors.forename: Lotfollah
authors.initials: L
authors.lastname: Saghaie
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Mansourian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D019713:Receptors, CCR5; D012243:Rhodopsin