RT Journal Article
SR Electronic
T1 The Inherent Flexibility of Receptor Binding Domains in SARS-CoV-2 Spike Protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.06.455384
DO 10.1101/2021.08.06.455384
A1 Hisham M. Dokainish
A1 Suyong Re
A1 Takaharu Mori
A1 Chigusa Kobayashi
A1 Jaewoon Jung
A1 Yuji Sugita
YR 2021
UL http://biorxiv.org/content/early/2021/08/06/2021.08.06.455384.abstract
AB Spike (S) protein is the primary antigenic target for neutralization and vaccine development for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It decorates the virus surface and undergoes large conformational changes of its receptor binding domain (RBD) to enter the host cell, as the abundant structural studies suggest. Here, we observe Down, one-Up, one-Open, and two-Up-like structures in enhanced molecular dynamics simulations without pre-defined reaction coordinates. The RBDA transition from Down to one-Up is supported by transient salt-bridges between RBDA and RBDC and by the glycan at N343B. Reduced interactions between RBDA and RBDB induce the RBDB motions toward two-Up. Glycan shielding for neutralizing antibodies is the weakest in one-Open. Cryptic pockets are revealed at the RBD interfaces in intermediate structures between Down and one-Up. The inherent flexibility in S-protein is, thus, essential for the structure transition and shall be considered for antiviral drug rational design or vaccine development.Competing Interest StatementThe authors have declared no competing interest.