Fig. 2. Computational design of CXCR4 associations with specific conformations.

a Mutations designed to selectively stabilize the CXCR4 open-dimer conformation without affecting CXCR4 monomer stability were identified in the extracellular and TMH regions. b Mutations designed to selectively stabilize the CXCR4 closed-dimer conformation without affecting CXCR4 monomer stability were identified in the extracellular region. Key atomic contacts are represented as red dotted lines. c Schematic conformational energy landscapes of CXCR4 dimerization in the inactive and active states for the open-dimer stabilizing designs. d Schematic conformational energy landscapes of CXCR4 dimerization in the inactive and active states for the closed-dimer stabilizing designs. c, d The dimerization energies reported in Supplementary Table 1 were used to plot the energy landscapes. The monomer energies and energy barriers between states are fictitious and were not predicted by our simulations. e Ranking of the CXCR4 variants based on changes in buried surface area upon dimerization (ΔSASA) calculated from the predicted models in the active state. The ΔSASA is reported for the most occupied dimer conformation for each variant: L194R open-dimer state, WT open-dimer state, N192W closed-dimer state, W195L closed-dimer state. Larger buried ΔSASA are predicted to correlate with enhanced dimerization propensity (see Supplementary Table 2).