Objective: To model a 3D-structure of Thymic Stromal Lymphopoietin (TSLP) and docking of small molecules for development of novel natural anti-allergic drug. Method: Crystal structure of the Mus musculus cytokine receptor (Protein Data Bank ID: 4NN5) was used as template for comparative modeling in MODELLER (v 9.16). Loop refinement of the modeled structure was performed in MODELLER and further verified and analyzed using Ramachandaran plot and ERRAT. Molecules from ZINC Natural product database were randomly docked into the predicted model using Autodock 4.2 program. Molecules with lower binding affinity were filtered based on molecular descriptors of Wlogp < 5 and TPSA < 140 Å² and further assessed for pharmacokinetics and bioavailability property using Boiled egg model, and later checked for mutagenic, tumorigenic, reproductive effect and irritant toxicity analysis. Results: The modeled 3-D structure of TSLP has shown a good quality model with 91.2% at the most favored region by Ramachandran statistics and 86.4 overall qualities of ERRAT evaluations. Six molecules were selected as top hits by passing the filtering criteria and their binding interaction of hydrophilic, hydrophobic and pi-cation with the target. They have good pharmacokinetic properties with high gastro-intestinal absorption, the toxicity analysis shows all the six molecules to have non-mutagenic, non-tumorigenic and non-reproductive effect. Conclusion: This work predict the 3D structure of TSLP using comparative modelling methods. Six ligands were identified with high binding energy by molecular docking approaches and optimized to have good gastrointestinal absorption and non-toxic. They can be good oral drugs against allergic diseases.
Key words: Allergy, TSLP, Modeling, Natural, Drugs, Pharmacokinetics.