Fragment Molecular Orbital Based Interaction Analyses on COVID-19 Main Protease - Inhibitor N3 Complex (PDB ID: 6LU7)

Ryo Hatada, Koji Okuwaki, Yuji Mochizuki, Yuma Handa, Kaori Fukuzawa, Yuto Komeiji, Yoshio Okiyama, Shigenori Tanaka

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

The worldwide spread of COVID-19 (new coronavirus found in 2019) is an emergent issue to be tackled. In fact, a great amount of works in various fields have been made in a rather short period. Here, we report a fragment molecular orbital (FMO) based interaction analysis on a complex between the SARS-CoV-2 main protease (Mpro) and its peptide-like inhibitor N3 (PDB ID: 6LU7). The target inhibitor molecule was segmented into five fragments in order to capture site specific interactions with amino acid residues of the protease. The interaction energies were decomposed into several contributions, and then the characteristics of hydrogen bonding and dispersion stabilization were made clear. Furthermore, the hydration effect was incorporated by the Poisson-Boltzmann (PB) scheme. From the present FMO study, His41, His163, His164, and Glu166 were found to be the most important amino acid residues of Mpro in interacting with the inhibitor, mainly due to hydrogen bonding. A guideline for optimizations of the inhibitor molecule was suggested as well based on the FMO analysis.

Original languageEnglish
Pages (from-to)3593-3602
Number of pages10
JournalJournal of chemical information and modeling
Volume60
Issue number7
DOIs
Publication statusPublished - 2020 Jul 27
Externally publishedYes

ASJC Scopus subject areas

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

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