title: Structural Evaluation and Binding Mode Analysis of CCL19 and CCR7 Proteins-Identification of Novel Leads for Rheumatic and Autoimmune Diseases: An Insilico study.
abstract: The Human Chemokine (C-C motif) ligand 19 (CCL19) protein plays a major role in rheumatic and autoimmune diseases. The 3D models of the CCL19 and its receptor CCR7 are generated using homology modeling and are validated using standard computational protocols. Disulfide bridges identified in 3D model of CCL19 protein give extra stability to the overall protein structure. The active site region of protein CCL19, containing N-terminal amino acid residues (Gly22 to Leu31), is predicted using in silico techniques. Protein-protein docking studies are carried out between the CCL19 and CCR7 proteins to analyse the active site binding interactions of CCL19. The binding domain of CCL19 is subjected to structure-based virtual screening of small molecule databases, and identified several bioisosteric ligand molecules having pyrrolidone and piperidone pharmacophores. The prioritized ligands with acceptable ADME properties are reported as new leads for the design of potential CCL19 antagonists for rheumatic and autoimmune disease therapies.
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Santhi Prada
authors.initials: SP
authors.lastname: Vellanki
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Ramasree
authors.initials: R
authors.lastname: Dulapalli
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Kondagari
authors.affiliation: Department of Chemistry, Post Graduate College of Science, Saifabad, Osmania University, Hyderabad, Telangana State, 500004, India.
authors.forename: Navaneetha
authors.initials: N
authors.lastname: Nambigari
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Rajender
authors.initials: R
authors.lastname: Vadija
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Ramatenki
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Rama Krishna
authors.initials: RK
authors.lastname: Dumpati
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Tarnaka, Hyderabad, Telangana State, 500007, India. vuma@osmania.ac.in.
authors.forename: Uma
authors.initials: U
authors.lastname: Vuruputuri
mesh_terms: D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000188:drug therapy*; D020134:Catalytic Domain; D054415:Chemokine CCL19 / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D017124:Conserved Sequence; D004220:Disulfides / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D054400:Receptors, CCR7 / Q000737:chemistry* / Q000378:metabolism*; D012216:Rheumatic Diseases / Q000188:drug therapy*; D012997:Solvents; D040681:Structural Homology, Protein
chemical_list: D054415:Chemokine CCL19; D004220:Disulfides; D008024:Ligands; D054400:Receptors, CCR7; D012997:Solvents
keywords: Chemokine CCL19; Homology modeling; Protein–protein docking and virtual screening