Molecular dynamics simulations of various coronavirus main proteinases.
Identifieur interne : 000903 ( Ncbi/Checkpoint ); précédent : 000902; suivant : 000904Molecular dynamics simulations of various coronavirus main proteinases.
Auteurs : H-L Liu [Taïwan] ; J-C Lin ; Y. Ho ; W-C Hsieh ; C-W Chen ; Y-C SuSource :
- Journal of biomolecular structure & dynamics [ 0739-1102 ] ; 2004.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : Cysteine Endopeptidases.
- enzymology : Coronavirus 229E, Human, SARS Virus.
- Amino Acid Sequence, Binding Sites, Computer Simulation, Drug Design, Humans, Molecular Sequence Data, Protein Structure, Secondary, Sequence Alignment.
Abstract
In this study, two homology models (denoted as MproST and MproSH) 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.
DOI: 10.1080/07391102.2004.10506982
PubMed: 15214807
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular dynamics simulations of various coronavirus main proteinases.</title><author><name sortKey="Liu, H L" sort="Liu, H L" uniqKey="Liu H" first="H-L" last="Liu">H-L Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemical Engineering and Graduate Institute of Biotechnology, National Taipei University of Technology, 1 Section 3 Chung-Hsiao East Road, Taipei, Taiwan 10608. f10894@ntut.edu.tw</nlm:affiliation><country wicri:rule="url">Taïwan</country></affiliation></author><author><name sortKey="Lin, J C" sort="Lin, J C" uniqKey="Lin J" first="J-C" last="Lin">J-C Lin</name></author><author><name sortKey="Ho, Y" sort="Ho, Y" uniqKey="Ho Y" first="Y" last="Ho">Y. Ho</name></author><author><name sortKey="Hsieh, W C" sort="Hsieh, W C" uniqKey="Hsieh W" first="W-C" last="Hsieh">W-C Hsieh</name></author><author><name sortKey="Chen, C W" sort="Chen, C W" uniqKey="Chen C" first="C-W" last="Chen">C-W Chen</name></author><author><name sortKey="Su, Y C" sort="Su, Y C" uniqKey="Su Y" first="Y-C" last="Su">Y-C Su</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2004">2004</date><idno type="RBID">pubmed:15214807</idno><idno type="pmid">15214807</idno><idno type="doi">10.1080/07391102.2004.10506982</idno><idno type="wicri:Area/PubMed/Corpus">002D07</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002D07</idno><idno type="wicri:Area/PubMed/Curation">002D07</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002D07</idno><idno type="wicri:Area/PubMed/Checkpoint">002B92</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002B92</idno><idno type="wicri:Area/Ncbi/Merge">000903</idno><idno type="wicri:Area/Ncbi/Curation">000903</idno><idno type="wicri:Area/Ncbi/Checkpoint">000903</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Molecular dynamics simulations of various coronavirus main proteinases.</title><author><name sortKey="Liu, H L" sort="Liu, H L" uniqKey="Liu H" first="H-L" last="Liu">H-L Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemical Engineering and Graduate Institute of Biotechnology, National Taipei University of Technology, 1 Section 3 Chung-Hsiao East Road, Taipei, Taiwan 10608. f10894@ntut.edu.tw</nlm:affiliation><country wicri:rule="url">Taïwan</country></affiliation></author><author><name sortKey="Lin, J C" sort="Lin, J C" uniqKey="Lin J" first="J-C" last="Lin">J-C Lin</name></author><author><name sortKey="Ho, Y" sort="Ho, Y" uniqKey="Ho Y" first="Y" last="Ho">Y. Ho</name></author><author><name sortKey="Hsieh, W C" sort="Hsieh, W C" uniqKey="Hsieh W" first="W-C" last="Hsieh">W-C Hsieh</name></author><author><name sortKey="Chen, C W" sort="Chen, C W" uniqKey="Chen C" first="C-W" last="Chen">C-W Chen</name></author><author><name sortKey="Su, Y C" sort="Su, Y C" uniqKey="Su Y" first="Y-C" last="Su">Y-C Su</name></author></analytic><series><title level="j">Journal of biomolecular structure & dynamics</title><idno type="ISSN">0739-1102</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Binding Sites</term><term>Computer Simulation</term><term>Coronavirus 229E, Human (enzymology)</term><term>Cysteine Endopeptidases (chemistry)</term><term>Drug Design</term><term>Humans</term><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>SARS Virus (enzymology)</term><term>Sequence Alignment</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term><term>Conception de médicament</term><term>Coronavirus humain 229E (enzymologie)</term><term>Cysteine endopeptidases ()</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Simulation numérique</term><term>Sites de fixation</term><term>Structure secondaire des protéines</term><term>Séquence d'acides aminés</term><term>Virus du SRAS (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus humain 229E</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Coronavirus 229E, Human</term><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Binding Sites</term><term>Computer Simulation</term><term>Drug Design</term><term>Humans</term><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>Sequence Alignment</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term><term>Conception de médicament</term><term>Cysteine endopeptidases</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Simulation numérique</term><term>Sites de fixation</term><term>Structure secondaire des protéines</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In this study, two homology models (denoted as MproST and MproSH) 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.</div></front></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><noCountry><name sortKey="Chen, C W" sort="Chen, C W" uniqKey="Chen C" first="C-W" last="Chen">C-W Chen</name><name sortKey="Ho, Y" sort="Ho, Y" uniqKey="Ho Y" first="Y" last="Ho">Y. Ho</name><name sortKey="Hsieh, W C" sort="Hsieh, W C" uniqKey="Hsieh W" first="W-C" last="Hsieh">W-C Hsieh</name><name sortKey="Lin, J C" sort="Lin, J C" uniqKey="Lin J" first="J-C" last="Lin">J-C Lin</name><name sortKey="Su, Y C" sort="Su, Y C" uniqKey="Su Y" first="Y-C" last="Su">Y-C Su</name></noCountry><country name="Taïwan"><noRegion><name sortKey="Liu, H L" sort="Liu, H L" uniqKey="Liu H" first="H-L" last="Liu">H-L Liu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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