Methyl Ferulate Induced Conformational Changes of DeOxyHbS: Implication on Sickle Erythrocyte Polymerization

Sickle cell disease (SCD) is a molecular disease caused by substituting glutamic acid with valine at the β-6 position of the hemoglobin, leading to the polymerization of erythrocytes that contain the hemoglobin afterward leads to severe clinical consequences. Polymerization of sickle hemoglobin occurs only in the deoxygenated form i.e only sickle deoxyhemoglobin (DeOxyHbS) polymerizes. SCD is predominant in children living in Africa, especially in West Africa. Therefore, molecular docking and molecular dynamic simulation studies were carried out on methyl ferulate isolated from Ficus thonningii leaves, a known antisickling plant used in Eastern Nigeria to manage SCD. The Harborne procedure was used for extraction, whereas the combination of column chromatography and flash chromatography was used for the isolation and purification of active principles of the leaves extract. The structure of methyl ferulate was determined based on nuclear magnetic resonance (NMR) analysis. A binding affinity of -5.8 kcal/mol indicated that methyl ferulate binds to DeOxyHbS and could interfere with the processes that trigger sickle hemoglobin polymerization in vitro. The observed variations in perturbation of both DeOxyHbS and FTH3-DeOxyHbS complex root mean square deviation (RMSD), the radius of gyration (Rgyr), solvent accessible surface area (SASA), potential energy (PE), and Van der Waal’s (VDW) interactions were obtained from the molecular dynamic simulation studies of the binding site amino acid residue performed at         500 ps and suggest that in silico methyl ferulate binds with amino acid residues reported being involved in sickle hemoglobin polymerization and thus may possess antisickling potentials in vitro.