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

Journal of Chemical Information and Modeling
Ryo HatadaShigenori Tanaka

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.

References

Oct 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Haitao YangZihe Rao
Nov 17, 2006·Journal of Computational Chemistry·Dmitri G Fedorov, Kazuo Kitaura
Mar 14, 2012·Physical Chemistry Chemical Physics : PCCP·Dmitri G FedorovKazuo Kitaura
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Feb 26, 2020·Journal of Chemical Theory and Computation·Alexander HeifetzAndrea Townsend-Nicholson
Mar 21, 2020·Journal of Computational Chemistry·Yoshinobu AkinagaYuji Mochizuki

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Citations

Jul 17, 2020·Antimicrobial Agents and Chemotherapy·Hui-Chen HungJohn Tsu-An Hsu
Dec 22, 2020·Briefings in Bioinformatics·Vaishali P WamanChristine Orengo
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sebastián A CuestaEdgar A Márquez
Mar 13, 2021·Physical Chemistry Chemical Physics : PCCP·Ernest Awoonor-Williams, Abd Al-Aziz A Abu-Saleh
Aug 23, 2020·Microorganisms·Qingxin Li, CongBao Kang
Mar 31, 2021·Journal of Chemical Information and Modeling·Giorgio AmendolaSandro Cosconati
Mar 30, 2021·Chemical Physics Letters·Adnan Cetin
Apr 30, 2021·Parasitology International·Nobuaki YasuoMasakazu Sekijima
Jun 15, 2021·The Journal of Physical Chemistry. B·Shigenori TanakaYuji Mochizuki
Jul 3, 2021·Chemical Society Reviews·Eugene N MuratovAlexander Tropsha
Aug 18, 2021·Computational and Structural Biotechnology Journal·Ponciano García-GutiérrezJorge Garza
Aug 5, 2020·Combinatorial Chemistry & High Throughput Screening·Samir ChtitaTahar Lakhlifi

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Methods Mentioned

BETA
X-ray

Software Mentioned

PIEDA
IFIE
FMOe
Pair Interaction Energy Decomposition Analysis ( PIEDA )
ABINIT
FMO
MOE
MP

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