Computational Prediction for the Binding Affinity of Interleukins 3 and 5 and GM- CSF to Cell Surface Receptors on Human Eosinophils

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 14.477 kD glycoprotein comprising 144 amino acids residues. The respective encoding gene is located on chromosome 5 in human. This protein stimulates proliferation and differentiation of macrophages. N-terminally seventeen amino acid residues are serving as a signal peptide while, the rest of 127 amino acids, known to have therapeutics application, is termed Molgramostim. Previous studies have revealed a high affinity of this protein for binding to a heterodimer receptor on surface of the cell. The respective receptor includes α and β chains which the β chain is similar to interleukins 3 and 5 receptors. Due to this similarity, interleukins 3 and 5 are capable to compete with GM-CSF in binding to the shared receptor. In the present study, to evaluate the binding affinity of interleukins 3 and 5 and GM-CSF to the same receptor, a computational prediction study carried out using Modeller, Hex and Molegro softwares. According to the results, interleukin 3 with -517.09 kJ/mole, interleukin 5 with -538.05 kJ/mole and GM-CSF with - 606.17 kJ/mole energy could bind to the α and β chains of receptor. In the next step the two chains of the receptor were separated and the affinity of each protein to both chains was studied. Based on the results the binding affinity of all three considered proteins to α chain of the protein was weaker than the binding to β chain. The binding energy of interleukin 3, interleukin 5 and GM-CSF to β chain of receptors was -620.37 kJ/mole,-663.80 kJ/mole and -696.07 kJ/mole respectively. According to the results, interleukin 3 and interleukin 5 strongly compete with GM-CSF in binding to cell surface receptors on human eosinophils.