Computational Analysis of the SARS-CoV-2 RBD-ACE2-Binding Process Based on MD and the 3D-RISM Theory

J Chem Inf Model. 2022 Jun 13;62(11):2889-2898. doi: 10.1021/acs.jcim.2c00192. Epub 2022 May 18.

Abstract

The binding process of angiotensin-converting enzyme 2 (ACE2) to the receptor-binding domain (RBD) of the severe acute respiratory syndrome-like coronavirus 2 spike protein was investigated using molecular dynamics simulation and the three-dimensional reference interaction-site model theory. The results suggested that the protein-binding process consists of a protein-protein approaching step, followed by a local structural rearrangement step. In the approaching step, the interprotein interaction energy decreased as the proteins approached each other, whereas the solvation free energy increased. As the proteins approached, the glycan of ACE2 first established a hydrogen bond with the RBD. Thereafter, the number of interprotein hydrogen bonds increased rapidly. The solvation free energy increased because of the desolvation of the protein as it approached its partner. The spatial distribution function of the solvent revealed the presence of hydrogen bonds bridged by water molecules on the RBD-ACE2 interface. Finally, principal component analysis revealed that ACE2 showed a pronounced conformational change, whereas there was no significant change in RBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2* / chemistry
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Binding Sites
  • COVID-19* / metabolism
  • COVID-19* / virology
  • Humans
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Domains
  • SARS-CoV-2* / metabolism
  • Spike Glycoprotein, Coronavirus* / chemistry
  • Spike Glycoprotein, Coronavirus* / metabolism

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2