EFFECT OF TOLL-LIKE RECEPTOR INHIBITOR IMIQUIMOD ON IL1R1 INTERACTION WITH IL-1RA AND ITS SNP VARIANT-AN IN SILICO APPROACH
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2016, Vol 8, Issue 5
Abstract
Objective: Interleukin 1 receptor antagonist (IL1Ra) acts as an antagonist to Interleukin 1 beta (IL1β) signalling in maintaining homeostasis. A loss of function due to Single Nucleotide Polymorphism (SNP) occurrence in IL1Ra can lead to dysregulated state as seen in autoimmune disease pathogenesis. The current study aims at achieving conformational stability in the IL1R1-IL1Ra_SNP complex by introducing a ligand into the region apart from the active site of Interleukin 1 receptor type1 (IL1R1).Methods: Protein-protein docking was performed using ClusPro, for IL1R1 with IL1β, IL1Ra and IL1Ra_SNP variant to study the difference in the interaction between the complexes. A known inhibitor, Imiquimod was docked using Glide, to the Il1R1-IL1Ra_SNP complex using flexible docking and the change in surface energy was calculated.Results: Binding Interactions show that IL1Ra binds more avidly to IL1R1 than IL1β. Conformational instability was seen in the IL1R1-IL1Ra_SNP complex. The difference in the amino acid interactions between the IL1R1 with IL1Ra and IL1Ra_SNP variant further illustrated the change in binding residues and hydrogen bond formation. Upon docking of an appropriate ligand to the IL1R1-IL1Ra_SNP complex, the conformational stability of the IL1R1-IL1Ra_SNP complex enhanced considerably suggesting a possible mechanism for treating SNP-induced conformational instability.Conclusion: Toll-like receptors like IL1R1 have many binding pockets apart from its active site. No strategies have yet been reported in targeting them for correcting conformational instability induced by SNP. Through our study, it was observed that the conformational instability of IL1R1-IL1Ra_SNP complex decreased upon introducing an appropriate small molecule.Keywords: IL1β, IL1R1, IL1Ra, SNP
Authors and Affiliations
Anand Thiyagaraj, Jithin S. Sunny, Waheeta Hopper
DOSAGE RESPONSE OF PIMPINELLA TIRUPATIENSIS TUBEROUS ROOT EXTRACT ON HYPERGLYCEMIC CONDITION IN STZ- INDUCED DIABETIC RATS WITH REFERENCES TO SHORT AND LONG TERM TREATMENT
Objectives: To evaluate the antidiabetic effect of three extractions [n-Hexane (n-HE), ethyl alcohol (EAE) and aqueous extract (AE)] of Pimpinella tirupatiensis (Pt) tuberous root on the fasting blood glucose (FBG) level...
BENEFICIAL EFFECTS OF COFFEE AND MAINTENANCE OF URIC ACID LEVELS
Objective: This study aimed in finding out if drinking coffee over a long term showed a marked influence on the serum uric acid level and Fasting blood glucose level.Methods: The study population had 200 healthy subjects...
EXTEMPORANEOUS COMPOUNDING PRACTICE BY PHARMACISTS: A SYSTEMATIC REVIEW
Objective: To identify the frequency and scope of extemporaneous compounding practice reported in community and hospital pharmacies.Methods: A systematic literature review was undertaken to identify the prevalence of ext...
SAMPLE-A RAW DATA FOR FUTURE INFORMATION OF LIFE
Gene amplification requires a biological sample which is collected prior to the demands. The sample for such analysis plays a vital role as they serve as a resource for the core material-Deoxyribonucleic acid. A sample f...
EXTRACTION AND ISOLATION OF FLAVONOID QUERCETIN FROM THE LEAVES OF TRIGONELLA FOENUM-GRAECUM AND THEIR ANTI-OXIDANT ACTIVITY
Objective: The present study was designed for isolation of bioactive flavonoid molecule quercetin from the leaves of Trigonella foenum-graecum and their subsequent characterization. Methods: Crude extracts of fenugreek w...