Fig. 2: Structural characterization of spike opening and conformational masking for three spike homologues.

a, An example structure of SARS-CoV-2 spike protein from our simulations that is fully compatible with receptor binding, as shown by superimposing ACE2 (grey). The three chains of the spike protein are illustrated with a cartoon and transparent surface representation (orange, teal and purple), and glycans are shown as sticks (green). b, Three spike homologues have very different probabilities of adopting ACE2-binding-competent conformations, likely modulating their affinities for both ACE2 and antibodies that engage the ACE2-binding interface. HCoV-NL63, SARS-CoV-1 and SARS-CoV-2 are shown as light blue, orange and black, respectively. c, The probability distribution of the spike opening for each homologue. Opening is quantified in terms of how far the centre of mass of an RBD deviates from its position in the closed (or down) state. The cryptic epitope for the antibody CR3022 (red) is only accessible to antibody binding in extremely open conformations. d, Our simulations capture exposure of cryptic epitopes that are buried in the up and down cryoEM structures. The fraction of residues within different epitopes that are exposed to a 0.5 nm radius probe for the down structure (blue), up structure (yellow), the ensemble average from our simulations (green) and the maximum value we observe in our simulations (red). Epitopes are determined as the residues that contact the specified antibody and are clustered by their binding location on the RBD¹³.