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

Norio Yoshida, Yutaka Maruyama, Ayori Mitsutake, Akiyoshi Kuroda, Ryo Fujiki, Kodai Kanemaru, Daisuke Okamoto, Alexander E. Kobryn, Sergey Gusarov, Haruyuki Nakano

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2889-2898
Number of pages10
JournalJournal of Chemical Information and Modeling
Issue number11
Publication statusPublished - Jun 13 2022

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences


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