Melero Roberto, Sorzano Carlos Oscar S, Foster Brent, Vilas José-Luis, Martínez Marta, Marabini Roberto, Ramírez-Aportela Erney, Sanchez-Garcia Ruben, Herreros David, Del Caño Laura, Losana Patricia, Fonseca-Reyna Yunior C, Conesa Pablo, Wrapp Daniel, Chacon Pablo, McLellan Jason S, Tagare Hemant D, Carazo Jose-Maria
Centro Nacional de Biotecnologia-CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain.
Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
IUCrJ. 2020 Sep 29;7(Pt 6):1059-69. doi: 10.1107/S2052252520012725.
Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, stable spike conformations, but virtually a continuum of states. An ensemble map was obtained with minimum bias, from which the extremes of the change along the direction of maximal variance were modeled by flexible fitting. The results provide a warning of the potential image-processing classification instability of these complicated data sets, which has a direct impact on the interpretability of the results.
通过一种基于新共识的图像处理方法并结合主成分分析，对处于融合前状态的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的灵活性和构象动力学进行了分析。这些研究揭示了在先前表征的1-RBD向上状态周围涉及受体结合结构域（RBD）、N端结构域以及结构域1和2的协同运动，这些运动已被建模为弹性变形。结果表明，在该数据集中不存在明确界定的、稳定的刺突蛋白构象，而实际上是一个连续的状态集合。通过最小偏差获得了一个总体图谱，从中通过灵活拟合对沿最大方差方向变化的极值进行了建模。这些结果警示了这些复杂数据集在图像处理分类方面可能存在的不稳定性，这对结果的可解释性有直接影响。
