Fig 1.
N-Terminal Domain (NTD), Receptor Binding Domain (RBD), Subunit 1/Subunit 2 junction (S1/S2), Fusion Peptide (FP), Heptad Repeat 1 (HR1), Heptad Repeat 2 (HR2), Transmembrane Domain (TM), and the Cytoplasmic Tail (CT). Crystallography structure in the conformational state of all 3 RBD domains closed (PDB 6VXX) and of 1 RBD open (PDB 6VYB), binding to ACE2 (PDB 6M17).
Fig 2.
Two-state Markov chain of Spike protein conformations.
Fig 3.
Dynamical Signature clustering for the closed (A) and open (B) state structures for WT and 22 mutants from GISAID (S1 Table). The clustering measures the distance between each pair of Dynamical Signature. Different colors were used to identify branches within a threshold of similarity (8.7 and 3.2 for closed and open state, respectively). The branches that comprehend most strains containing the D614G mutation are highlighted in red.
Fig 4.
Effects of the D614G mutation on the Dynamical Signature of the closed (purple) and open B chain RBD (blue) structures, measured by the difference between the calculated b-factors of D614 and G614.
Chains are represented in different colours and the position of the mutation is marked in yellow, using the same colours as for different regions of the structure as represented in the colours of the structures.
Fig 5.
Comparison between SARS-CoV-2 and SARS-CoV.
Dynamical Signature difference of the closed (purple) and open B chain RBD (blue) between aligned residues of the Spike protein from SARS-CoV-2 and SARS-CoV, with SARS-CoV chains represented in the top bar and equivalent colors in the structures and SARS-CoV-2 chains represented in the bar just below.
Fig 6.
Heatmaps representing the values of ΔSvib for the closed structure (A, left-hand section) and for the open structure (A, right-hand section), and the values of VDS (B) for every possible mutant in Spike from positions 14 to 913. Each column represents one of the 20 amino acids (repeated in the left heatmap). Notice that for each position (represented in a row), one particular column represents the value of the WT amino acid found at that position. Higher values of ΔSvib are represented in yellow and lower values in dark purple. Higher values of VDS are represented in red and lower values in blue. The domain structure of Spike is represented in (C) for reference purposes.
Fig 7.
VDS values represented in the structure of Spike from two angles according to the median value for each position and the same color scheme as in the Difference Score Heatmap (Fig 6B).
Fig 8.
Difference in the occupancies for the open and the closed states (open–closed) for six variants of the Spike protein.
Experimental values are represented on the Y-axis and the predicted values in the scale on the X-axis. Predicted values for the parameters k = 0.5, γ = 0.001. Represented linear fit of Experimental = 192.011*Predicted + 92.9013. Errors on the experimental measurements are not known.
Table 1.
Putative mutations, associated VDS (ΔSvib (open)− ΔSvib (close), in units of J.K-1) and predicted occupancies for the open and closed states for the mutants with predicted open-state occupancy higher than that of the wild type.
Predicted occupancy values are shown for the open conformation, the closed conformation, and the difference between the two (closed–open). The data for the remaining mutants with occupancy below that of the wild type but VDS>0.3 (red) as well as those with the lowest predicted VDS values (blue) is presented in S3 Table.
Table 2.
Experimental and predicted occupancies for the open and closed states and their difference for multiple SARS-CoV-2 variants.
Experimental values obtained from Gobeil et al. [30] and Xiong et al. [34].
Fig 9.
(A) Difference in the occupancies for the open and the closed states for the top 64 mutants with VDS>0.3 (red) and the 20 mutants with lower VDS (blue). Occupancy difference for the WT is represented by the dashed green line. Y-axis based on the transformation of a symmetric logarithmic scale. (B) Two visualizations of the 6VYB structure highlighting the mutations. The bottom 20 mutant positions are marked in two shades of blue, with the darker shade indicating positions in which at least one mutant had an (open–closed) occupancy value smaller than wild type. The top 64 mutant positions are marked in two shades of red, with the darker shade indicating positions in which at least one mutant had an (open–closed) occupancy value higher than wild type.