Extended Data Fig. 10: Dynamics of HKU1 spike S1^A.

All MD simulations performed with the Caen1 (a) and N1 sequence (b) were combined for an RMSD analysis based on the holo cryo-EM model as a reference structure. Conformational changes from the apo into the holo state are apparent as transitions from high (red) to low (blue) RMSD states. Simulations performed with the N1 strain sequence were based on the apo cryo-EM model of Caen1, replacing respective residues different in N1. Individual simulations (a: 33, b: 69) are separated by vertical lines. The spontaneous conformational shifts of the e1 loop, observed in the simulations starting with the disialoside (PSA2) bound to the apo cryo-EM conformation of the Caen1 and N1 spike proteins are indicated with red arrows. Simulations based on the holo EM model with PSA2 or other Neu5,9Ac-containing ligands show ligand-induced stabilisation of the e1 conformational shift.