Biological profiling of anti-HIV agents and insight into CCR5 antagonist binding using in silico techniques.

Molecular requirements and determinants for efficient binding to CCR5 were interpreted by computational techniques based on comparative receptor structure modeling, advanced 3D-QSAR, docking, and shape-based virtual screening of commercially available entry blockers. Results of this study may be valuable for predicting new HIV entry-blocking leads.Acquired immune deficiency syndrome (AIDS) is responsible for more than 31 million deaths, and many more people are affected by this disease worldwide. Novel ligands that are capable of blocking virus-cell fusion are emerging as promising candidate molecules against HIV-1 infection because they have the promise to overcome the major drawbacks of classical highly active antiretroviral (HAART) drugs. However, structure-based design continues to be hampered owing to the paucity of experimentally determined 3D information about HIV-1 cell-surface co-receptors. Using computational techniques based on comparative receptor structure modeling, advanced 3D-QSAR, and protein-ligand docking, we present recent results that define updated molecular requirements and determinants for efficient binding of small-molecule ligands to CCR5, a principal biological target for HIV entry blockers. These results are compared with shape- and property-based virtual screening results for commercially available entry blockers, and will be valuable for predicting new HIV entry-blocking leads.