A preliminary step in the SARS-CoV-2 human infection process is a conformational change of the receptor binding domain (RBD) of its spike protein, characterized by a significant loss of symmetry. During this process, the residues which later on bind to the human angiotensin converting enzyme 2 (ACE2) receptor, become exposed at the surface of the protein. Symmetry analysis of a data set of 33 protein structures from experimental measurements and 32 structures from molecular dynamics simulation, show that the initial state carries clear indications on the structure of the final state, with respect to the local distortion along the sequence. This surprising finding implies that this type of analysis predicts the mechanism of change. We further show that the level of local distortion at the initial state increases with variant's transmissibility, for the wild type (WT) along with past and present variants of concern (WT ∼ alpha < beta < delta < Omicron BA.1), in accordance with the trend of their evolutionary path. In other words, the initial structure of the variant which is most infectious is also the most distorted, making its path to the final state shorter. It has been claimed that the RBD migration of the spike protein is allosterically controlled. Our analysis provides a quantitative support to a major theorem in this respect - that information about an allosteric process is encoded in the structure itself, suggesting that the path of local distortion is related to an allosteric information network.
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© 2023 The Royal Society of Chemistry.
- Molecular Dynamics Simulation
- Protein Binding
- Spike Glycoprotein, Coronavirus