Molecular dynamics simulations of various coronavirus main proteinases

Hsuan Liang Liu, Jin Chung Lin, Yih Ho, Wei Chan Hsieh, Chin Wen Chen, Yuan Chen Su

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In this study, two homology models (denoted as MproST and M proSH) of main proteinase (Mpro) from the novel coronavirus associated with severe acute respiratory syndrome (SARS-CoV) were constructed based on the crystal structures of Mpro from transmissible gastroenteritis coronavirus (TGEV) (MproT) and human coronavirus HcoV-229E (MproH), respectively. Both MproST and MproSH exhibit similar folds as their respective template proteins. These homology models reveal three distinct functional domains as well as an intervening loop connecting domains II and III as found in both template proteins. A catalytic cleft containing the substrate binding sites S1 and S2 between domains I and II are also observed. S2 undergoes more significant structural fluctuation than S1 during the 400 ps molecular dynamics simulations because it is located at the open mouth of the catalytic cleft, while S1 is situated in the very bottom of this cleft. The thermal unfolding of these proteins begins at domain III, where the structure is least conserved among these proteins. MPro may still maintain its proteolytic activity while it is partially unfolded. The electrostatic interaction between Arg40 and Asp186 plays an important role in maintaining the structural integrity of both S1 and S2.

Original languageEnglish
Pages (from-to)65-77
Number of pages13
JournalJournal of Biomolecular Structure and Dynamics
Volume22
Issue number1
Publication statusPublished - Aug 2004

Fingerprint

Molecular Dynamics Simulation
Human Coronavirus 229E
SARS Virus
Severe Acute Respiratory Syndrome
Protein Unfolding
Coronavirus
Proteins
Gastroenteritis
Static Electricity
Mouth
Peptide Hydrolases
Hot Temperature
Binding Sites
Coronavirus 3C-like proteinase

Keywords

  • Coronavirus
  • Homology
  • Main Proteinase
  • Molecular dynamics simulations
  • Severe acute respiratory syndrome (SARS)
  • Substrate binding site

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Liu, H. L., Lin, J. C., Ho, Y., Hsieh, W. C., Chen, C. W., & Su, Y. C. (2004). Molecular dynamics simulations of various coronavirus main proteinases. Journal of Biomolecular Structure and Dynamics, 22(1), 65-77.

Molecular dynamics simulations of various coronavirus main proteinases. / Liu, Hsuan Liang; Lin, Jin Chung; Ho, Yih; Hsieh, Wei Chan; Chen, Chin Wen; Su, Yuan Chen.

In: Journal of Biomolecular Structure and Dynamics, Vol. 22, No. 1, 08.2004, p. 65-77.

Research output: Contribution to journalArticle

Liu, HL, Lin, JC, Ho, Y, Hsieh, WC, Chen, CW & Su, YC 2004, 'Molecular dynamics simulations of various coronavirus main proteinases', Journal of Biomolecular Structure and Dynamics, vol. 22, no. 1, pp. 65-77.
Liu, Hsuan Liang ; Lin, Jin Chung ; Ho, Yih ; Hsieh, Wei Chan ; Chen, Chin Wen ; Su, Yuan Chen. / Molecular dynamics simulations of various coronavirus main proteinases. In: Journal of Biomolecular Structure and Dynamics. 2004 ; Vol. 22, No. 1. pp. 65-77.
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