Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen

Table 1 Docking of the small molecule Nef antagonist DQBS to HIV-1 Nef

Binding site	Binding energy (kcal/mol)	Nef residues within 4 Å of DQBS
Nef dimer
1	−9.0	Nef subunit 1 (blue in Figure 8): Gln104, Asp108, Pro122, Asp123
		Nef subunit 2 (green in Figure 8): Gln104, Asp108, Gln107, Asp111, Leu112, Pro122, Gln125, Asn126, Tyr127
2	−8.3	Pro78, Met79, Thr80, Tyr81, Asp123, Trp124, Asn126, Leu137, Thr138, Phe129, Tyr202
Nef monomer
1	−7.9	Gln104, Gln107, Gln125, Asn126, Tyr127, Thr128, Pro129, Arg134, Leu137, Tyr202
2	−7.9	Met79, Tyr82, Asn126, Leu137, Thr138, Phe139, His193, Tyr202, Phe203
3	−7.7	Leu91, Lys94, Gly95, Gly96, Leu97, Leu100, Arg106, Ile109, Leu110, Trp113

Docking was performed using AutoDock Vina and an X-ray crystal structure of HIV-1 Nef as described under Materials and Methods. For the Nef dimer, two binding sites were predicted, with a preference for the dimer interface site (Site 1). Analysis using a single Nef monomer from this crystal structure returned three energetically equivalent sites. The table summarizes the binding energies and predicted binding site residues within 4 Å of the docked ligand. Molecular models for the two sites predicted from the Nef dimer are shown in Figure 8.

ISSN: 1742-4690