Structural Evaluation and Binding Mode Analysis of CCL19 and CCR7 Proteins—Identification of Novel Leads for Rheumatic and Autoimmune Diseases: An Insilico study

• Published in: Interdisciplinary sciences : computational life sciences Vol. 10; no. 2; pp. 346 - 366
• Main Authors: Vellanki, Santhi Prada, Dulapalli, Ramasree, Kondagari, Bhargavi, Nambigari, Navaneetha, Vadija, Rajender, Ramatenki, Vishwanath, Dumpati, Rama Krishna, Vuruputuri, Uma
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018; Springer Nature B.V
• Subjects: Amino Acid Sequence; Amino acids; Antagonists; Autoimmune diseases; Autoimmune Diseases - drug therapy; Binding; Biomedical and Life Sciences; Catalytic Domain; CC chemokine receptors; CCL19 protein; CCR7 protein; Chemokine CCL19 - chemistry; Chemokine CCL19 - metabolism; Computational Biology/Bioinformatics; Computational Science and Engineering; Computer Appl. in Life Sciences; Computer applications; Computer Simulation; Conserved Sequence; Disulfides - metabolism; Docking; Drug Evaluation, Preclinical; Health Sciences; Homology; Humans; Life Sciences; Ligands; Mathematical and Computational Physics; Medicine; Molecular chains; Molecular Docking Simulation; Molecular structure; Original Research Article; Pharmacology; Pharmacophores; Protein Binding; Protein Domains; Protein structure; Protein Structure, Secondary; Proteins; Receptors, CCR7 - chemistry; Receptors, CCR7 - metabolism; Rheumatic Diseases - drug therapy; Solvents; Statistics for Life Sciences; Structural Homology, Protein; Theoretical; Theoretical and Computational Chemistry; Three dimensional models; Protein–protein docking and virtual screening; Chemokine CCL19; Homology modeling
• ISSN: 1913-2751; 1867-1462
• DOI: 10.1007/s12539-017-0212-0

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.