Research and Development by

Yuji Sugita, RIKEN

Corresponding Research Area

BioMedical Counter-measures: Analysis of CT scans for early detection and avoidance of severe illness, monitoring of patients with mild illness, prediction of risk of severe illness, understanding of the effects of viral mutation, etc.


Visualization of the 3D structure of spike protein 1/2

■Understanding of the spike protein’s three-dimensional (3D)-structure on the surface of the severe acute respiratory syndrome coronavirus 2 is important for the development of drugs and vaccines

■Visualizing carbohydrate chains on the surface of the spike protein using cryo-electron microscopy is difficult

■Clarifying the motions and structures of carbohydrate chains by visualizing molecular dynamics simulation results and elucidating their role in structural changes to the active form


  

Movement of carbohydrate chains on the surface of spike protein in the inactive form (left) and active form (right)[video]

Results of molecular dynamics calculations using supercomputer “Fugaku” are visualized as a video

→ Movements of these carbohydrate chains are essential for binding to and dissociation from antibodies

Contacts and hydrogen bonds between carbohydrate chains and amino acids on the spike protein surface in the inactive form and active form estimated and visualized by simulations

These serve as indicators of hydrophobic interactions caused by van der Waals forces

Courtesy of RIKEN

Visualization of the 3D structure of spike protein 2/2

■Movements of carbohydrate chains when the inactive form is converted to the active form

→ The visualized structures indicated that amino acid residues, including N165 and N234 (asparagine residues with a carbohydrate chain; in the figure below, orange and yellow balls are carbohydrate chains), are crucial for structural changes

* A protein is a substance in which 20 different amino acids are linked in tandem (the order of amino acids is called the amino acid sequence). Carbohydrate chains linked to amino acids affect the protein properties. Asparagine is one such amino acid.

Movements of carbohydrate chains when the inactive form is converted into the active form

Visualized structures indicated that amino acid residues, including N165 and N234, are essential for structural changes

Changes in the distance between carbohydrate chains (red) and amino acids when the inactive form (RMSD = 7A) is forcibly converted into the active form (RMSD = 0) by Steered molecular dynamics

→Infection will not occur if the intramolecular interactions shown in the yellow text boxes can be inhibited by drugs/vaccines

Courtesy of RIKEN