SARS-CoV-2 Main Protease: A Molecular Dynamics Study

Journal of Chemical Information and Modeling
Dimas Suárez, Natalia Díaz

Abstract

Herein, we investigate the structure and flexibility of the hydrated SARS-CoV-2 main protease by means of 2.0 μs molecular dynamics (MD) simulations in explicit solvent. After having performed electrostatic pKa calculations on several X-ray structures, we consider both the native (unbound) configuration of the enzyme and its noncovalent complex with a model peptide, Ace-Ala-Val-Leu-Gln∼Ser-Nme, which mimics the polyprotein sequence recognized at the active site. For each configuration, we also study their monomeric and homodimeric forms. The simulations of the unbound systems show that the relative orientation of domain III is not stable in the monomeric form and provide further details about interdomain motions, protomer-protomer interactions, inter-residue contacts, accessibility at the catalytic site, etc. In the presence of the peptide substrate, the monomeric protease exhibits a stable interdomain arrangement, but the relative orientation between the scissile peptide bond and the catalytic dyad is not favorable for catalysis. By means of comparative analysis, we further assess the catalytic impact of the enzyme dimerization, the actual flexibility of the active site region, and other structural effects induced by substrate...Continue Reading

References

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Citations

Feb 3, 2021·Journal of Biomolecular Structure & Dynamics·Mustafa Tekpinar, Ahmet Yildirim
Feb 11, 2021·Colloids and Surfaces. A, Physicochemical and Engineering Aspects·Kazushige Yokoyama, Akane Ichiki
Apr 27, 2021·The Journal of Physical Chemistry Letters·Laura Zanetti-PolziIsabella Daidone
May 5, 2021·Chemical Communications : Chem Comm·Natalia Díaz, Dimas Suárez
May 28, 2021·Frontiers in Molecular Biosciences·Shafi MahmudMd Abu Saleh
Jun 8, 2021·Journal of Chemical Information and Modeling·Daniel J EvansAlbert Y Lau
May 25, 2021·Journal of Traditional and Complementary Medicine·Ahmed A ZakiAhmed A Al-Karmalawy
Jun 15, 2021·Journal of Chemical Information and Modeling·Eunice ChoShozeb Haider
Jun 15, 2021·The Journal of Physical Chemistry. B·Shigenori TanakaYuji Mochizuki
Jun 26, 2021·Molecular Diversity·Henrique S FernandesNuno M F S A Cerqueira
Jul 20, 2021·Journal of Chemical Information and Modeling·Jingyi YangWeiwei Xue
Jun 19, 2021·ChemMedChem·Ulises Martínez-OrtegaRodrigo Aguayo-Ortiz
Jul 31, 2021·Scientific Reports·Gabriel Jiménez-AvalosUNKNOWN COVID-19 Working Group in Perú
Jul 29, 2021·The Journal of Physical Chemistry. B·Aditya K PadhiTimir Tripathi
Aug 6, 2021·PLoS Computational Biology·Natália TeruelRafael J Najmanovich
Jan 1, 2021·Journal of Chemical Information and Modeling·Adrian J Mulholland, Rommie E Amaro
Aug 28, 2020·Journal of Chemical Information and Modeling·Olivier Sheik AmamuddyÖzlem Tastan Bishop
Aug 28, 2021·Antibiotics·Muhammad Fayyaz Ur RehmanMehwish Aslam
Sep 1, 2021·Current Opinion in Virology·Peter Eugene JonesJodi A Hadden-Perilla
Sep 14, 2021·Journal of Biomolecular Structure & Dynamics·Glaucio Monteiro FerreiraAntti Poso

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Methods Mentioned

BETA
surface plasmon resonance
isothermal titration calorimetry
X-ray

Software Mentioned

CPPTRAJ
SANDER
PMEMD
2Pep
tLEaP
APBS
AMBER18
CENCALC
ff14SB
DSSP

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