Fig. 3: Cryo-EM structure of the ACE2–RBD-62 complex at 2.9 Å resolution.
From: SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution
a, Cartoon representation of the Cryo-EM structure of ACE2 (cyan) in complex with RBD-62 RBM (magenta) with the RBD-62 mutations resolved in the density (orange spheres). b, The S477N, Q498R and N501Y mutations depicted in the RBM (orange spheres) interact with S19, Q42 and K353 of ACE2 (cyan spheres), respectively. These interacting residues are located at the two extremes of the RBD–ACE2 interface, stabilizing the complex. c,d, Molecular details of selected interactions depicted in the left (c) and right (d) grey boxes in b contributing to higher affinity. c, The presence of E484K and S477N causes repositioning of the RBD-62 loop between amino acids 475 and 487. The loop of RBD-WT is shown for comparison (PDB ID 6M17 in white and 6M0J in pale yellow). The change of main chain positions moves F486 to the optimum position for methionine–aromatic interaction50. d, The interaction network formed between RBD-62 mutated residues and ACE2. e, Open book presentation of ACE2 and RBD-WT and RBD-62. The electrostatic potential was calculated using the program UCSF Chimera v1.13, with negative potential in red and positive in blue. Electrostatic complementarity between RBD and ACE2 is strengthened in RBD-62 by positive charges at V445K, N460K, E484K and Q498R. The black line on ACE2 indicates the RBD-binding site.
