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

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Chemical Information and Modeling 2020-07, Vol.60 (7), p.3593-3602
Main Authors: Hatada, Ryo, Okuwaki, Koji, Mochizuki, Yuji, Handa, Yuma, Fukuzawa, Kaori, Komeiji, Yuto, Okiyama, Yoshio, Tanaka, Shigenori
Format: Article
Language:English
Subjects:
Betacoronavirus - enzymology
Computational Biochemistry
Coronavirus 3C Proteases
Coronaviruses
COVID-19
Cysteine Endopeptidases - chemistry
Cysteine Endopeptidases - metabolism
Hydrogen bonding
Inhibitors
Molecular Docking Simulation
Molecular orbitals
Protease
Protease Inhibitors - metabolism
Protein Binding
Protein Conformation
Residues
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Viral Nonstructural Proteins - antagonists & inhibitors
Viral Nonstructural Proteins - chemistry
Viral Nonstructural Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1549-9596
1549-960X
DOI:10.1021/acs.jcim.0c00283