A Computational Study of PADI4 Receptor for Identifying Novel Drug Target against Rheumatoid Arthritis

Abstract

Tooba Qamar32949, Prekshi Garg32950 and Prachi Srivastava32951*

Background and objectives: Rheumatoid arthritis is an autoimmune disorder in which the immune system of the body loses the capability to differentiate between self and non-self cells. Patients with this disorder have autoantibodies like anti-citrullinated peptide antibody, which target their own healthy cells. PADI4 (Protein-Arginine Deiminase type-4) protein is found to be involved in pathophysiology of this disease, hence this protein was selected as a target for further studies. Till date only symptomatic treatments are available rather than permanent cure against it, hence research in such area is highly promising. The current in silico approach is based on identification of novel therapeutic inhibitors against PADI4 receptor using the computational researches.

Methods: In current study, the human Peptidyl Arginine Deiminase 4 (PADI4) receptor is the selected target in reference to designing of drug inhibitor against the Rheumatoid Arthritis. The 3D structure of the receptor was obtained from Protein Data Bank (PDB). A molecular docking study was performed between group of natural and synthetic compounds which possess proven anti-rheumatic activity with PADI4 receptor using Autodock tool 1.5.6.

Results: On the basis of parameters like lowest binding energy (kcal/Mol),hydrogen bond interaction, conformational structure, the three compounds namely Hydroxyanthroquinone(-7.40 kcal/mol), thymol (-5.97 kcal/mol), and vallinic acid (-5.90 kcal/mol) were screened out that shows very strong binding affinity with the active site of PADI4 receptor.

Interpretation and conclusion: The study concludes the high potential of hydroxyanthroquinone, thymol and vallinic acid to be active inhibitors against the PADI4 receptor protein. Thus, the molecular docking study will help in better understanding of the molecular interaction between ligand and receptor binding site thereby leading to development of novel therapeutics that can be considered as a prophylactic approach against this disease.