Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. Since gp120 plays a vital role in the ability of HIV-1 to enter CD4+ cells, its evolution is of particular interest. Many neutralizing antibodies bind to sites located in variable regions of gp120, so mutations in these regions will be selected for strongly. A conserved region in the gp120 glycoprotein that is involved in the metastable attachment of gp120 to CD4 has been identified and targeting of invariant region has been achieved with a broadly neutralising antibody, IgG1-b12. CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structur.