PMC:7553147 / 32151-36194 JSONTXT 7 Projects

Annnotations TAB TSV DIC JSON TextAE

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.