Impact of the CXCR4 structure on docking-based virtual screening of HIV entry inhibitors

Studying the binding interactions of allosteric agonists and antagonists of the CXCR4 receptor

“…The use of LigandFit 71 docking functions in our previous work 34 showed very good results when screening a test set of CXCR4 actives and decoys by DockScore scoring function. Moreover, regarding the evaluation of pose prediction, self-docking the cognate ligands showed also LigandFit as one of the best performing functions, principally for structures 3ODU and 3OE6.…”

“…Moreover, regarding the evaluation of pose prediction, self-docking the cognate ligands showed also LigandFit as one of the best performing functions, principally for structures 3ODU and 3OE6. Hence, LigandFit docking function was used to divide the main binding site applying 3 partition levels, which created 6 binding subsites, according to our previous work 34 .…”

Probing the Molecular Interactions between CXC Chemokine Receptor 4 (CXCR4) and an Arginine-Based Tripeptidomimetic Antagonist (KRH-1636)

“…not based on any experimentally verified ligand-receptor interactions. Moreover, when the X-ray structure of CXCR4 33 was revealed in 2010 it showed that bovine rhodopsin was a poor template for CXCR4, 64 questioning the validity of the previously proposed binding models for the small molecule peptide-based antagonists.…”

Anti-HIV Drug Development Through Computational Methods

“…The structures provide new clues about the interactions between CXCR4 and SDF-1α and with gp120 (49). Thereafter, a receptor-based virtual screening performance of the five crystallized CXCR4 structures along with a CXCR4 rhodopsin-based homology model was carried out using 248 known CXCR4 inhibitors from four different chemotype families and 4,696 different presumed inactives (50). The results showed that the 3OE6 structure achieved the highest docking-based performance and was proposed as the best for CXCR4 antagonist discovery via virtual screening (50).…”