Homology models and molecular dynamics simulations of main proteinase from coronavirus associated with Severe Acute Respiratory Syndrome (SARS)

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In this study, two structural models (denoted as MproST and MproSH) of the main proteinase (Mpro) from the novel coronavirus associated with severe acute respiratory syndrome (SARS-CoV) were constructed based on the crystallographic structures of Mpro from transmissible gastroenteritis coronavirus (TGEV) (MproT) and human coronavirus HcoV-229E (MproH), respectively. Various 200 ps molecular dynamics simulations were subsequently performed to investigate the dynamics behaviors of several structural features. Both MproST and M proSH exhibit similar folds as their respective template proteins. These structural models reveal three distinct functional domains as well as an intervening loop connecting domains II and III as found in both template proteins. In addition, domain III of these structures exhibits the least secondary structural conservation. A catalytic cleft containing the substrate binding subsites S1 and the S2 between domains I and II are also observed in these structural models. Although these structures share many common features, the most significant difference occurs at the S2 subsite, where the amino acid residues lining up this subsite are least conserved. It may be a critical challenge for designing anti-SARS drugs by simply screening the known database of proteinase inhibitors.

Original languageEnglish
Pages (from-to)889-900
Number of pages12
JournalJournal of the Chinese Chemical Society
Volume51
Issue number5 A
Publication statusPublished - 2004

Fingerprint

Molecular dynamics
Peptide Hydrolases
Computer simulation
Linings
Conservation
Screening
Proteins
Amino Acids
Substrates
Pharmaceutical Preparations
Coronavirus 3C-like proteinase

Keywords

  • Coronavirus
  • Functional domain
  • Inhibitor
  • Main proteinase
  • Molecular dynamics simulations
  • Severe acute respiratory syndrome (SARS)
  • Structural model

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Homology models and molecular dynamics simulations of main proteinase from coronavirus associated with Severe Acute Respiratory Syndrome (SARS). / Liu, Hsuan Liang; Lin, Jin Chung; Ho, Yih; Hsieh, Wei Chan; Chen, Chin Wen; Su, Yuan Chen.

In: Journal of the Chinese Chemical Society, Vol. 51, No. 5 A, 2004, p. 889-900.

Research output: Contribution to journalArticle

Liu, Hsuan Liang ; Lin, Jin Chung ; Ho, Yih ; Hsieh, Wei Chan ; Chen, Chin Wen ; Su, Yuan Chen. / Homology models and molecular dynamics simulations of main proteinase from coronavirus associated with Severe Acute Respiratory Syndrome (SARS). In: Journal of the Chinese Chemical Society. 2004 ; Vol. 51, No. 5 A. pp. 889-900.
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