Id |
Subject |
Object |
Predicate |
Lexical cue |
T222 |
0-2 |
Sentence |
denotes |
4. |
T223 |
4-17 |
Sentence |
denotes |
Conclusions |
T224 |
18-281 |
Sentence |
denotes |
In this work, we present a clear example of how the structural discovery process can be greatly accelerated by a wise combination of rapid data sharing and the use of the wave of newly developed algorithms that characterize this phase of the ‘cryo-EM revolution’. |
T225 |
282-473 |
Sentence |
denotes |
The reanalysis of the data used in Wrapp et al. (2020 ▸), but with new workflows and new tools, has resulted in a rich analysis of the spike flexibility as a key characteristic of the system. |
T226 |
474-647 |
Sentence |
denotes |
Essentially, and at least to a first approximation, the spike moves in a continuous manner with no preferential states, as clearly shown in the scatter plots in Fig. 3 ▸(b). |
T227 |
648-825 |
Sentence |
denotes |
In this way, the result of a particular instance of image-processing analysis, including a 3D classification, should be regarded as a snapshot of this quasi-continuum of states. |
T228 |
826-1078 |
Sentence |
denotes |
In our case, we have shown that a particular meta image-classification approach, implemented through a consensus among different methods in many steps of the analysis, results in classes that are at the extreme of the main axis of variance in PC space. |
T229 |
1079-1311 |
Sentence |
denotes |
Clearly, PC1, through the analysis of the two extreme classes, reflects a concerted motion of the NTD–RBD–SD1–SD2 thumb, although there are smaller collective movements throughout the spike (see Fig. 2 ▸ and Supplementary Movie S1). |
T230 |
1312-1448 |
Sentence |
denotes |
In this case, the RBD moves together with the NTD, with a smaller degree of independent flexibility and always in the ‘up’ conformation. |
T231 |
1449-1702 |
Sentence |
denotes |
The NTD–RBD movement can be characterized to a large degree as a rotation, but the different RBDs present a much more complex pattern of flexibility, indicating an important structural rearrangement [from elastic analysis (Fig. 2 ▸) and PCA (Fig. 3 ▸)]. |
T232 |
1703-1979 |
Sentence |
denotes |
The presence of quasi-solid body rotation hinges is clearly located between amino acids 318–326 and 588–595, which produce most of the displacement, together with other hinges between amino acids 330–335 and 527–531, which accompany a less pronounced ‘up’ movement of the RBD. |
T233 |
1980-2137 |
Sentence |
denotes |
However, there are other PC axes explaining significant fractions of the inter-image variance that are not properly explored at the level of our two classes. |
T234 |
2138-2328 |
Sentence |
denotes |
PC3 is a clear example, indicating a high variance at the voxels associated with RBD up, which probably suggests large conformational changes in this area that result in the RBD moving down. |
T235 |
2329-2682 |
Sentence |
denotes |
The flexibility analysis performed in this work complements previous analysis showing large rotations together with RBD up–down structural changes (Pinto et al., 2020 ▸; Wrapp et al., 2020 ▸), in the sense that the different studies present ‘snapshots’ of a continuum of movements obtained by a particular instance of an image-processing classification. |
T236 |
2683-2812 |
Sentence |
denotes |
In a sense, all of these results are correct, but none of them is able to capture the richness of the flexibility of this system. |
T237 |
2813-3050 |
Sentence |
denotes |
This fact reflects the intrinsic instability of segmenting a continuum into defined clusters, which is a clear limitation of the classification approaches that needs to be considered in detailed analysis of any data set from this system. |
T238 |
3051-3332 |
Sentence |
denotes |
An obvious way to increase the resolution of the moving parts of the spike is to reduce their mobility, as is the case, for instance, in the biochemical stabilization of Hsieh et al. (2020 ▸) and also in the formation of a complex with an antibody against NTD (Chi et al., 2020 ▸). |
T239 |
3333-3702 |
Sentence |
denotes |
On the other hand, the route towards a more complete analysis of the flexibility of the spike protein necessarily involves the analysis of data sets that are quite substantially larger than those being used in most current SARS-CoV-2 studies, so that all of the main axes of inter-image variability can be explored; this is work that is under development at the moment. |
T240 |
3703-4043 |
Sentence |
denotes |
From a biomedical perspective, the proof that a quasi-continuum of flexibility is a key characteristic of this specimen, a concept that has been implicitly considered in much of the structural work performed so far but never demonstrated, suggests that ways to interfere with this flexibility could be important components of new therapies. |