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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron is currently the most prevalent SARS-CoV-2 variant worldwide. Herein, we calculated molecular dynamics simulations of the trimeric spike WT  and Spike BA.1  for 300 ns. Our results show that Spike BA.1  has more conformational flexibility than Spike WT . Our principal component analysis (PCA) allowed us to observe a broader spectrum of different conformations for Spike BA.1 , mainly at N-terminal domain (NTD) and receptor-binding domain (RBD). Such increased flexibility could contribute to decreased neutralizing antibody recognition of this variant. Our molecular dynamics data show that the RBD BA.1  easily visits an up-conformational state and the prevalent D614G mutation is pivotal to explain molecular dynamics results for this variant because to lost hydrogen bonding interactions between the residue pairs K854 SC /D614 SC , Y837 MC /D614 MC , K835 SC /D614 SC , T859 SC /D614 SC . In addition, Spike BA.1  residues near the furin cleavage site are more flexible than in Spike WT , probably due to P681H and D614G substitutions. Finally, dynamical cross-correlation matrix (DCCM) analysis reveals that D614G and P681H may allosterically affect the cleavage site S1/S2. Conversely, S2' site may be influenced by residues located between NTD and RBD of a neighboring protomer of the Spike WT . Such communication may be lost in Spike BA.1 , explaining the changes of the cell tropism in the viral infection. In addition, the movements of the NTD WT  and NTD BA.1  may modulate the RBD conformation through allosteric effects. Taken together, our results explain how the structural aspects may explain the observed gains in infectivity, immune system evasion and transmissibility of the Omicron variant. Communicated by Ramaswamy H. Sarma

journal of biomolecular structure and dynamics

Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility