Flexibility and mobility of SARS-CoV-2-related protein structures

Sci Rep. 2021 Feb 19;11(1):4257. doi: 10.1038/s41598-021-82849-2.

Abstract

The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of possible SARS-CoV-2 drug targets, as deposited on the Protein Databank (PDB), and ascertain their dynamics, flexibility and rigidity. For example, for the SARS-CoV-2 spike protein-using its complete homo-trimer configuration with 2905 residues-our method identifies a large-scale opening and closing of the S1 subunit through movement of the S[Formula: see text] domain. We compute the full structural information of this process, allowing for docking studies with possible drug structures. In a dedicated database, we present similarly detailed results for the further, nearly 300, thus far resolved SARS-CoV-2-related protein structures in the PDB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Binding Sites
  • COVID-19 / epidemiology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Crystallography, X-Ray
  • Drug Development / methods*
  • Humans
  • Models, Molecular
  • Pandemics / prevention & control
  • Protein Binding
  • Protein Domains / drug effects
  • Protein Multimerization / drug effects
  • Protein Subunits / drug effects
  • Protein Subunits / metabolism
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Spike Glycoprotein, Coronavirus / drug effects
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Spike Glycoprotein, Coronavirus / ultrastructure

Substances

  • Antiviral Agents
  • Protein Subunits
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2