Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120

AIM: To investigate the interaction between human CCR5 receptors (CCR5) and HIV-1 envelope glycoprotein gp120 (HIV-1 gp120) and HIV-1 receptor CD4 ant igens (CD4). METHODS: The structurally con served regions (SCR) of human CC R5 was built by the SYBYL/Biopolymer module using the corresponding transme mbrane (TM) domain of bacteriorhodopsin (bR) as the template. The coordinat es for amino-ter minal residue sequence, and carboxyl-terminal residue sequ ence, extracellular and cytoplasmic loops were generated using LOOP SEARCH algorithm. Subsequently the structural model was merged into the complex wi th HIV-1 gp120 and CD4. RESULTS: Human CCR5 interacted with both an HIV-1 g p120 and CD4. The N-terminal residues (especially Met1 and Gln4) of human C CR5, contacted with CD4 residues, mainly 7Nith one span (56 - 59) of CD4 in electrostatic interaction and hydrogen-bonds. The binding sites of human C CR5 were buried in a hydrophobic center surrounded by a highly basic periph ery. On the other hand, direct interatomic contacts were made between ? CCR 5 residues and 6 gp120 amino-acid residues, which included van der Waals co ntacts, hydrophobic interaction, and hydrogen bonds. CONCLUSION: The intera ction model should be helpful for rational design of novel anti-HIV drugs.