ABSTRACT:
Background: Sickle cell disease is an autosomal recessive disorder caused due to point mutation on a single gene on chromosome 11 resulting in substitution of valine in place of glutamic acid at sixth position of beta-chain of adult hemoglobin (HbA). The purpose of the current study is to evaluate the effectiveness of phytochemicals (Rutin and its derivatives) for antisickling effects. Methods: The structure of Rutin is obtained in Simplified Molecular Input Line Entry System (SMILES) format and is subjected to chemical similarity search using Extended-connectivity fingerprints (ECFP4) fingerprints. The Tanimoto coefficient is used as the similarity metric and top compounds obtained on chemical similarity search are further subjected to molecular docking based screening analysis. A local database of phytochemicals is created using the IMPAAT database. Molecular docking approach is implemented using iGEMDOCK for screening and ranking of Rutin and its derivatives. The docking is implemented with standard docking protocol with population size of 200 and number of generations= 70. Results: All the ligand molecules showed acceptable binding energies with the 2HBS receptor molecule ranging between -124.87 to-79.59kcal/mol. Koprutin showed the highest binding affinity against the 2HBS (2HBS-DEOXYHEMOGLOBIN S) and which can be further developed as an antisickling agent. Conclusion: The integration of insilico modelling techniques with the wet lab based experimental methods can significantly reduce the cost in terms of time and other resources. Further the intricacies of molecular interactions taking place between ligands and receptors can be better understood with the help of molecular modelling techniques.