TY - JOUR
T1 - Fragment Molecular Orbital Based Interaction Analyses on COVID-19 Main Protease - Inhibitor N3 Complex (PDB ID: 6LU7)
AU - Hatada, Ryo
AU - Okuwaki, Koji
AU - Mochizuki, Yuji
AU - Handa, Yuma
AU - Fukuzawa, Kaori
AU - Komeiji, Yuto
AU - Okiyama, Yoshio
AU - Tanaka, Shigenori
N1 - Funding Information:
The present work was supported by Ministry of Education, Culture, Sports, Science and Technology (MEXT) as a social and scientific priority issue #6 (Accelerated Development of Innovative Clean Energy Systems) to be tackled by using post-K computer (“Fugaku”) and also by Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from Japan Agency for Medical Research and Development (AMED) under Grant No. JP19am0101113. Additional supports were provided by the Rikkyo SFR and Kakenhi-JP19K12010. Y.M. acknowledges Mr. Takaya Abe and Mr. Kazuki Akisawa for their assistance. Lastly, it would be noted that almost all of the computations were carried out on the Fujitsu FX100 supercomputer at Nagoya University.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/7/27
Y1 - 2020/7/27
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jcim.0c00283
DO - 10.1021/acs.jcim.0c00283
M3 - Article
C2 - 32539372
AN - SCOPUS:85088517184
SN - 0095-2338
VL - 60
SP - 3593
EP - 3602
JO - Journal of Chemical Documentation
JF - Journal of Chemical Documentation
IS - 7
ER -