Fig. 7: Effect of G protein on the energy minima.

Exploration of the BFES starting from the lowest energy dimers containing an active CCR5 receptor and an inactive CCR5/CXCR4 protein embedded in the realistic plasma membrane model. aCCR5(G) represents an activated CCR5 protein bound to CCL3 and the Gαβγ heterotrimer. A aCCR5(G)–CCR5. D aCCR5(G)–CXCR4. The white dashed lines represent the boundaries of the CV regions explored by each system during over 50 μs of CG–MD simulations. These regions are denoted as A^G and B^G to distinguish them from the minima identified for the inactive receptors in the absence of G protein. The backmapped centroids of the A and B minima extracted after clusterization of the aCCR5(G)–CCR5 trajectories are represented as color-coded cartoons, respectively, on the right of (B, C). On the left of each panel, the corresponding centroids obtained from the initial MetaD–CG calculations with the inactive receptors are reported. Similarly, the backmapped centroids of the A and B minima extracted after clusterization of the aCCR5(G)–CXCR4 trajectories are represented as color-coded cartoons on the right of (E, F). On the left of each panel, the corresponding centroids obtained from the initial MetaD–CG calculations with the inactive receptors are reported.