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Table S1. Intermolecular interactions between the V3 tips and CCR5.

Figure S3. Structure and dynamics of free V3 from the MVC-Sens (grey) or MVC-Res (black) isolates. (A) Time series of root mean square deviation (RMSD) values for all atoms of the V3 loops, using as reference the average coordinates computed from the five independent simulations. (B) The phi and psi angular fluctuations were calculated and averaged by residue for every 25 ps segment of the five molecular dynamics trajectories. Standard deviations are reported for phi (top) and psi (bottom) backbone torsion angles. (C) The average RMS fluctuations (RMSF) were calculated for the carbon alpha atoms of the V3 loop residues from the ensemble of structures after superimposition of residues 296 to 330 (complete V3 loop, plain lines) or superimposition of residues 308 to 315 (V3 tip, dotted lines).

Figure S4. Western blot analysis of gp120 and Gag p24 expression on MVC-Sens, MVC-Res, MVC-Sens(V3R) and MVC-Res(V3S) viral particles. Three hundred ng Gag p24 of the different viral isolates were solubilized in lysis buffer (100 mM (NH4)2SO4, 20 mM Tris-HCl (pH 7.5), 10 % glycerol, and 1% Triton X-100) and then loaded onto Biorad CriterionTM XT 4-12% Bis-Tris Gels under reducing conditions. Virus-associated gp120 and p24 were visualized using a sheep anti-HIV-1 gp120 polyclonal antibody (AALTO Bio Reagents LTD.) and a mouse anti-HIV-1 p24 monoclonal antibody (clone 183-H12-5C) (NIH AIDS Reagent Program), respectively, and then with the appropriate HRP-conjugated secondary antibodies (VECTOR). Bands were developed by enhanced chemiluminescence (Thermo Scientific) and were quantified using a LAS-1000 CCD camera (Image Gauge Software, Fuji Film Co., Tokyo, Japan). The figure shows that the viral isolates have gp120/p24 ratios R that are in the same range (R = 1, 1.15, 1.24 and 0.81 for MVC-Sens, MVC-Res, MVC-Sens(V3R) and MVC-Res(V3S), respectively). A representative experiment out of two is shown.

Figure S5. Molecular modeling of the complex between CCR5 and MVC-Sens V3. The graphic shows time series of RMSD values of the complex using as reference the input coordinates. The table indicates which constraints or restraints were imposed on the system during the simulation. bb : backbone atoms, all : all atoms, sc : side chains.

Supplemental text (related to Figure 7 and additional file 4).

Figure S6. Molecular modeling of the complex between MVC-bound CCR5 and MVC-Res V3. The graphic shows time series of RMSD values of the complex using as reference the input coordinates. The table indicates which constraints or restraints were imposed on the system during the simulation. bb : backbone atoms, all : all atoms, sc : side chains.