Structural Evaluation and Binding Mode Analysis of CCL19 and CCR7 Proteins-Identification of Novel Leads for Rheumatic and Autoimmune Diseases: An Insilico study.
Interdiscip Sci
; 10(2): 346-366, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-28271460
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Simulação por Computador
/
Doenças Reumáticas
/
Quimiocina CCL19
/
Receptores CCR7
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
Idioma:
En
Revista:
Interdiscip Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Índia