Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41
HL9 is a nonapeptide fragment of human lysozyme which has been shown to have anti-HIV-1 activity in nanomolar concentration. This study aims to explain this inhibitory activity by using molecular dynamics (MD) simulation, focusing on the ectodomain of gp41, the envelope glycoprotein of HIV-1 crucial...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (6), p.1607-1611 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1611 |
|---|---|
| container_issue | 6 |
| container_start_page | 1607 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 21 |
| creator | Hartono, Yossa Dwi Lee, Angelina Noviani Lee-Huang, Sylvia Zhang, Dawei |
| description | HL9 is a nonapeptide fragment of human lysozyme which has been shown to have anti-HIV-1 activity in nanomolar concentration. This study aims to explain this inhibitory activity by using molecular dynamics (MD) simulation, focusing on the ectodomain of gp41, the envelope glycoprotein of HIV-1 crucial to membrane fusion. It was found that in HL9, two Trp residues separated by two others occupy the conserved hydrophobic pocket on gp41 and thus inhibit fusion in dominant-negative manner. Detailed HL9-gp41 binding interactions and free energies of binding were obtained through MD simulation and solvated interaction energies (SIE) calculation, giving a binding free energy of −8.25
kcal/mol which is in close agreement with the experimental value of −9.96
kcal/mol. Since C-helical region (C34) of gp41 also has two Trp residues separated by two others, this arrangement may be generalised and used to scan peptide library and to find those having similar manner of inhibition. |
| doi_str_mv | 10.1016/j.bmcl.2011.01.121 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_907158903</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X11001557</els_id><sourcerecordid>907158903</sourcerecordid><originalsourceid>FETCH-LOGICAL-c441t-b532a304114cbef86fafb5beff090dfe039a5aedbd92e32a4b4c7bac9c0ed62e3</originalsourceid><addsrcrecordid>eNqFkcGO0zAQhiMEYsvCC3AAXxCXTRjHdhpLe0EV0JUqcYBF3CzHGRdXiR1iB6k8Pa5a4AYnj-xv_rHmK4rnFCoKtHlzqLrRDFUNlFZAK1rTB8WK8oaXjIN4WKxANlC2kn-9Kp7EeACgHDh_XFzVlDHeSrYq_CaM05J0csHrgcS09EcSLOmc753fx1O93ckboonPxIRTcj0SO-v9iD6dnr8to_ZkOMbw8zjiDUmBbO--lJTYJeZUMs0hofNkP3H6tHhk9RDx2eW8Lu7fv_u82Za7jx_uNm93peGcprITrNYMOKXcdGjbxmrbiVxZkNBbBCa10Nh3vawxo7zjZt1pIw1g3-Sr6-L1OTcP_75gTGp00eAwaI9hiUrCmopWAvsv2QohoWVincn6TJo5xDijVdPsRj0fFQV1EqIO6iREnYQooCoLyU0vLvFLN2L_p-W3gQy8ugA6Gj3kxXrj4l-OyUY0DDL38sxZHZTez5m5_5QniWyVcdHUmbg9E5gX-8PhrKJx6A32bkaTVB_cv376C7Y3swM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>855908357</pqid></control><display><type>article</type><title>Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Hartono, Yossa Dwi ; Lee, Angelina Noviani ; Lee-Huang, Sylvia ; Zhang, Dawei</creator><creatorcontrib>Hartono, Yossa Dwi ; Lee, Angelina Noviani ; Lee-Huang, Sylvia ; Zhang, Dawei</creatorcontrib><description>HL9 is a nonapeptide fragment of human lysozyme which has been shown to have anti-HIV-1 activity in nanomolar concentration. This study aims to explain this inhibitory activity by using molecular dynamics (MD) simulation, focusing on the ectodomain of gp41, the envelope glycoprotein of HIV-1 crucial to membrane fusion. It was found that in HL9, two Trp residues separated by two others occupy the conserved hydrophobic pocket on gp41 and thus inhibit fusion in dominant-negative manner. Detailed HL9-gp41 binding interactions and free energies of binding were obtained through MD simulation and solvated interaction energies (SIE) calculation, giving a binding free energy of −8.25
kcal/mol which is in close agreement with the experimental value of −9.96
kcal/mol. Since C-helical region (C34) of gp41 also has two Trp residues separated by two others, this arrangement may be generalised and used to scan peptide library and to find those having similar manner of inhibition.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2011.01.121</identifier><identifier>PMID: 21334893</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; Biological and medical sciences ; energy ; Fundamental and applied biological sciences. Psychology ; glycoproteins ; HIV Envelope Protein gp41 - metabolism ; HIV-1 gp41 ; HL9 ; Human immunodeficiency virus 1 ; Human lysozyme ; Humans ; hydrophobicity ; Interactions. Associations ; Intermolecular phenomena ; lysozyme ; membrane fusion ; Models, Molecular ; Molecular biophysics ; molecular dynamics ; Molecular Sequence Data ; Muramidase - chemistry ; Muramidase - metabolism ; Peptide Fragments - metabolism ; peptide libraries ; Protein Binding</subject><ispartof>Bioorganic & medicinal chemistry letters, 2011-03, Vol.21 (6), p.1607-1611</ispartof><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-b532a304114cbef86fafb5beff090dfe039a5aedbd92e32a4b4c7bac9c0ed62e3</citedby><cites>FETCH-LOGICAL-c441t-b532a304114cbef86fafb5beff090dfe039a5aedbd92e32a4b4c7bac9c0ed62e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2011.01.121$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23965630$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21334893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hartono, Yossa Dwi</creatorcontrib><creatorcontrib>Lee, Angelina Noviani</creatorcontrib><creatorcontrib>Lee-Huang, Sylvia</creatorcontrib><creatorcontrib>Zhang, Dawei</creatorcontrib><title>Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>HL9 is a nonapeptide fragment of human lysozyme which has been shown to have anti-HIV-1 activity in nanomolar concentration. This study aims to explain this inhibitory activity by using molecular dynamics (MD) simulation, focusing on the ectodomain of gp41, the envelope glycoprotein of HIV-1 crucial to membrane fusion. It was found that in HL9, two Trp residues separated by two others occupy the conserved hydrophobic pocket on gp41 and thus inhibit fusion in dominant-negative manner. Detailed HL9-gp41 binding interactions and free energies of binding were obtained through MD simulation and solvated interaction energies (SIE) calculation, giving a binding free energy of −8.25
kcal/mol which is in close agreement with the experimental value of −9.96
kcal/mol. Since C-helical region (C34) of gp41 also has two Trp residues separated by two others, this arrangement may be generalised and used to scan peptide library and to find those having similar manner of inhibition.</description><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>energy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>glycoproteins</subject><subject>HIV Envelope Protein gp41 - metabolism</subject><subject>HIV-1 gp41</subject><subject>HL9</subject><subject>Human immunodeficiency virus 1</subject><subject>Human lysozyme</subject><subject>Humans</subject><subject>hydrophobicity</subject><subject>Interactions. Associations</subject><subject>Intermolecular phenomena</subject><subject>lysozyme</subject><subject>membrane fusion</subject><subject>Models, Molecular</subject><subject>Molecular biophysics</subject><subject>molecular dynamics</subject><subject>Molecular Sequence Data</subject><subject>Muramidase - chemistry</subject><subject>Muramidase - metabolism</subject><subject>Peptide Fragments - metabolism</subject><subject>peptide libraries</subject><subject>Protein Binding</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGO0zAQhiMEYsvCC3AAXxCXTRjHdhpLe0EV0JUqcYBF3CzHGRdXiR1iB6k8Pa5a4AYnj-xv_rHmK4rnFCoKtHlzqLrRDFUNlFZAK1rTB8WK8oaXjIN4WKxANlC2kn-9Kp7EeACgHDh_XFzVlDHeSrYq_CaM05J0csHrgcS09EcSLOmc753fx1O93ckboonPxIRTcj0SO-v9iD6dnr8to_ZkOMbw8zjiDUmBbO--lJTYJeZUMs0hofNkP3H6tHhk9RDx2eW8Lu7fv_u82Za7jx_uNm93peGcprITrNYMOKXcdGjbxmrbiVxZkNBbBCa10Nh3vawxo7zjZt1pIw1g3-Sr6-L1OTcP_75gTGp00eAwaI9hiUrCmopWAvsv2QohoWVincn6TJo5xDijVdPsRj0fFQV1EqIO6iREnYQooCoLyU0vLvFLN2L_p-W3gQy8ugA6Gj3kxXrj4l-OyUY0DDL38sxZHZTez5m5_5QniWyVcdHUmbg9E5gX-8PhrKJx6A32bkaTVB_cv376C7Y3swM</recordid><startdate>20110315</startdate><enddate>20110315</enddate><creator>Hartono, Yossa Dwi</creator><creator>Lee, Angelina Noviani</creator><creator>Lee-Huang, Sylvia</creator><creator>Zhang, Dawei</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110315</creationdate><title>Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41</title><author>Hartono, Yossa Dwi ; Lee, Angelina Noviani ; Lee-Huang, Sylvia ; Zhang, Dawei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-b532a304114cbef86fafb5beff090dfe039a5aedbd92e32a4b4c7bac9c0ed62e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amino Acid Sequence</topic><topic>Biological and medical sciences</topic><topic>energy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>glycoproteins</topic><topic>HIV Envelope Protein gp41 - metabolism</topic><topic>HIV-1 gp41</topic><topic>HL9</topic><topic>Human immunodeficiency virus 1</topic><topic>Human lysozyme</topic><topic>Humans</topic><topic>hydrophobicity</topic><topic>Interactions. Associations</topic><topic>Intermolecular phenomena</topic><topic>lysozyme</topic><topic>membrane fusion</topic><topic>Models, Molecular</topic><topic>Molecular biophysics</topic><topic>molecular dynamics</topic><topic>Molecular Sequence Data</topic><topic>Muramidase - chemistry</topic><topic>Muramidase - metabolism</topic><topic>Peptide Fragments - metabolism</topic><topic>peptide libraries</topic><topic>Protein Binding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hartono, Yossa Dwi</creatorcontrib><creatorcontrib>Lee, Angelina Noviani</creatorcontrib><creatorcontrib>Lee-Huang, Sylvia</creatorcontrib><creatorcontrib>Zhang, Dawei</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hartono, Yossa Dwi</au><au>Lee, Angelina Noviani</au><au>Lee-Huang, Sylvia</au><au>Zhang, Dawei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2011-03-15</date><risdate>2011</risdate><volume>21</volume><issue>6</issue><spage>1607</spage><epage>1611</epage><pages>1607-1611</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>HL9 is a nonapeptide fragment of human lysozyme which has been shown to have anti-HIV-1 activity in nanomolar concentration. This study aims to explain this inhibitory activity by using molecular dynamics (MD) simulation, focusing on the ectodomain of gp41, the envelope glycoprotein of HIV-1 crucial to membrane fusion. It was found that in HL9, two Trp residues separated by two others occupy the conserved hydrophobic pocket on gp41 and thus inhibit fusion in dominant-negative manner. Detailed HL9-gp41 binding interactions and free energies of binding were obtained through MD simulation and solvated interaction energies (SIE) calculation, giving a binding free energy of −8.25
kcal/mol which is in close agreement with the experimental value of −9.96
kcal/mol. Since C-helical region (C34) of gp41 also has two Trp residues separated by two others, this arrangement may be generalised and used to scan peptide library and to find those having similar manner of inhibition.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>21334893</pmid><doi>10.1016/j.bmcl.2011.01.121</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2011-03, Vol.21 (6), p.1607-1611 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_907158903 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amino Acid Sequence Biological and medical sciences energy Fundamental and applied biological sciences. Psychology glycoproteins HIV Envelope Protein gp41 - metabolism HIV-1 gp41 HL9 Human immunodeficiency virus 1 Human lysozyme Humans hydrophobicity Interactions. Associations Intermolecular phenomena lysozyme membrane fusion Models, Molecular Molecular biophysics molecular dynamics Molecular Sequence Data Muramidase - chemistry Muramidase - metabolism Peptide Fragments - metabolism peptide libraries Protein Binding |
| title | Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T09%3A56%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Computational%20study%20of%20bindings%20of%20HL9,%20a%20nonapeptide%20fragment%20of%20human%20lysozyme,%20to%20HIV-1%20fusion%20protein%20gp41&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Hartono,%20Yossa%20Dwi&rft.date=2011-03-15&rft.volume=21&rft.issue=6&rft.spage=1607&rft.epage=1611&rft.pages=1607-1611&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2011.01.121&rft_dat=%3Cproquest_cross%3E907158903%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=855908357&rft_id=info:pmid/21334893&rft_els_id=S0960894X11001557&rfr_iscdi=true |