Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization
Identifieur interne : 003752 ( Main/Exploration ); précédent : 003751; suivant : 003753Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization
Auteurs : Carl D. Elkin [États-Unis] ; Harmon J. Zuccola [États-Unis] ; James M. Hogle [États-Unis] ; Diane Joseph-Mccarthy [États-Unis]Source :
- Journal of Computer-Aided Molecular Design [ 0920-654X ] ; 2000-11-01.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- Algorithms, Amino Acid Sequence, Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Database Management Systems, Dimerization, Hepatitis Antigens (chemistry), Hepatitis Delta Virus (drug effects), Hepatitis Delta Virus (immunology), Protein Conformation, coiled-coil formation, d-peptide ligands, multiple copy simultaneous search (MCSS), structure-based drug design.
- MESH :
- chemical , chemistry : Antiviral Agents, Hepatitis Antigens.
- chemical , pharmacology : Antiviral Agents.
- drug effects : Hepatitis Delta Virus.
- immunology : Hepatitis Delta Virus.
- Algorithms, Amino Acid Sequence, Database Management Systems, Dimerization, Protein Conformation.
Abstract
Abstract: Hepatitis delta virus (HDV) encodes a single polypeptide called hepatitis delta antigen (DAg). Dimerization of DAg is required for viral replication. The structure of the dimerization region, residues 12 to 60, consists of an anti-parallel coiled coil [Zuccola et al., Structure, 6 (1998) 821]. Multiple Copy Simultaneous Searches (MCSS) of the hydrophobic core region formed by the bend in the helix of one monomer of this structure were carried out for many diverse functional groups. Six critical interaction sites were identified. The Protein Data Bank was searched for backbone templates to use in the subsequent design process by matching to these sites. A 14 residue helix expected to bind to the d-isomer of the target structure was selected as the template. Over 200 000 mutant sequences of this peptide were generated based on the MCSS results. A secondary structure prediction algorithm was used to screen all sequences, and in general only those that were predicted to be highly helical were retained. Approximately 100 of these 14-mers were model built as d-peptides and docked with the l-isomer of the target monomer. Based on calculated interaction energies, predicted helicity, and intrahelical salt bridge patterns, a small number of peptides were selected as the most promising candidates. The ligand design approach presented here is the computational analogue of mirror image phage display. The results have been used to characterize the interactions responsible for formation of this model anti-parallel coiled coil and to suggest potential ligands to disrupt it.
Url:
DOI: 10.1023/A:1008146015629
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000A45
- to stream Istex, to step Curation: 000A45
- to stream Istex, to step Checkpoint: 001051
- to stream Main, to step Merge: 003794
- to stream PubMed, to step Corpus: 002604
- to stream PubMed, to step Curation: 002604
- to stream PubMed, to step Checkpoint: 002451
- to stream Ncbi, to step Merge: 000077
- to stream Ncbi, to step Curation: 000077
- to stream Ncbi, to step Checkpoint: 000077
- to stream Main, to step Merge: 003669
- to stream Main, to step Curation: 003752
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization</title>
<author><name sortKey="Elkin, Carl D" sort="Elkin, Carl D" uniqKey="Elkin C" first="Carl D." last="Elkin">Carl D. Elkin</name>
</author>
<author><name sortKey="Zuccola, Harmon J" sort="Zuccola, Harmon J" uniqKey="Zuccola H" first="Harmon J." last="Zuccola">Harmon J. Zuccola</name>
</author>
<author><name sortKey="Hogle, James M" sort="Hogle, James M" uniqKey="Hogle J" first="James M." last="Hogle">James M. Hogle</name>
</author>
<author><name sortKey="Joseph Mccarthy, Diane" sort="Joseph Mccarthy, Diane" uniqKey="Joseph Mccarthy D" first="Diane" last="Joseph-Mccarthy">Diane Joseph-Mccarthy</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:C489559D93B9D694AB570E69C703A2A254D4A5B2</idno>
<date when="2000" year="2000">2000</date>
<idno type="doi">10.1023/A:1008146015629</idno>
<idno type="url">https://api.istex.fr/ark:/67375/VQC-WS2VWG99-R/fulltext.pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000A45</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A45</idno>
<idno type="wicri:Area/Istex/Curation">000A45</idno>
<idno type="wicri:Area/Istex/Checkpoint">001051</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001051</idno>
<idno type="wicri:doubleKey">0920-654X:2000:Elkin C:computational:design:of</idno>
<idno type="wicri:Area/Main/Merge">003794</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="RBID">pubmed:11131965</idno>
<idno type="wicri:Area/PubMed/Corpus">002604</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002604</idno>
<idno type="wicri:Area/PubMed/Curation">002604</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002604</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002451</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002451</idno>
<idno type="wicri:Area/Ncbi/Merge">000077</idno>
<idno type="wicri:Area/Ncbi/Curation">000077</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000077</idno>
<idno type="wicri:doubleKey">0920-654X:2000:Elkin C:computational:design:of</idno>
<idno type="wicri:Area/Main/Merge">003669</idno>
<idno type="wicri:Area/Main/Curation">003752</idno>
<idno type="wicri:Area/Main/Exploration">003752</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization</title>
<author><name sortKey="Elkin, Carl D" sort="Elkin, Carl D" uniqKey="Elkin C" first="Carl D." last="Elkin">Carl D. Elkin</name>
<affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Committee on Higher Degrees in Biophysics, Harvard University, 02139, Cambridge, MA</wicri:regionArea>
<orgName type="university">Université Harvard</orgName>
<placeName><settlement type="city">Cambridge (Massachusetts)</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zuccola, Harmon J" sort="Zuccola, Harmon J" uniqKey="Zuccola H" first="Harmon J." last="Zuccola">Harmon J. Zuccola</name>
<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 02115, Boston, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hogle, James M" sort="Hogle, James M" uniqKey="Hogle J" first="James M." last="Hogle">James M. Hogle</name>
<affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Committee on Higher Degrees in Biophysics, Harvard University, 02139, Cambridge, MA</wicri:regionArea>
<orgName type="university">Université Harvard</orgName>
<placeName><settlement type="city">Cambridge (Massachusetts)</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Joseph Mccarthy, Diane" sort="Joseph Mccarthy, Diane" uniqKey="Joseph Mccarthy D" first="Diane" last="Joseph-Mccarthy">Diane Joseph-Mccarthy</name>
<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Biological Chemistry Department, Wyeth Research, 87 CambridgePark Dr., 02140, Cambridge, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Journal of Computer-Aided Molecular Design</title>
<title level="j" type="abbrev">J Comput Aided Mol Des</title>
<idno type="ISSN">0920-654X</idno>
<idno type="eISSN">1573-4951</idno>
<imprint><publisher>Kluwer Academic Publishers</publisher>
<pubPlace>Dordrecht</pubPlace>
<date type="published" when="2000-11-01">2000-11-01</date>
<biblScope unit="volume">14</biblScope>
<biblScope unit="issue">8</biblScope>
<biblScope unit="page" from="705">705</biblScope>
<biblScope unit="page" to="718">718</biblScope>
</imprint>
<idno type="ISSN">0920-654X</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0920-654X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Algorithms</term>
<term>Amino Acid Sequence</term>
<term>Antiviral Agents (chemistry)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Database Management Systems</term>
<term>Dimerization</term>
<term>Hepatitis Antigens (chemistry)</term>
<term>Hepatitis Delta Virus (drug effects)</term>
<term>Hepatitis Delta Virus (immunology)</term>
<term>Protein Conformation</term>
<term>coiled-coil formation</term>
<term>d-peptide ligands</term>
<term>multiple copy simultaneous search (MCSS)</term>
<term>structure-based drug design</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Algorithmes</term>
<term>Antigènes d'hépatite virale ()</term>
<term>Antiviraux ()</term>
<term>Antiviraux (pharmacologie)</term>
<term>Conformation des protéines</term>
<term>Dimérisation</term>
<term>Systèmes de gestion de bases de données</term>
<term>Séquence d'acides aminés</term>
<term>Virus de l'hépatite delta ()</term>
<term>Virus de l'hépatite delta (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term>
<term>Hepatitis Antigens</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Hepatitis Delta Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Virus de l'hépatite delta</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Hepatitis Delta Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Algorithms</term>
<term>Amino Acid Sequence</term>
<term>Database Management Systems</term>
<term>Dimerization</term>
<term>Protein Conformation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Algorithmes</term>
<term>Antigènes d'hépatite virale</term>
<term>Antiviraux</term>
<term>Conformation des protéines</term>
<term>Dimérisation</term>
<term>Systèmes de gestion de bases de données</term>
<term>Séquence d'acides aminés</term>
<term>Virus de l'hépatite delta</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Abstract: Hepatitis delta virus (HDV) encodes a single polypeptide called hepatitis delta antigen (DAg). Dimerization of DAg is required for viral replication. The structure of the dimerization region, residues 12 to 60, consists of an anti-parallel coiled coil [Zuccola et al., Structure, 6 (1998) 821]. Multiple Copy Simultaneous Searches (MCSS) of the hydrophobic core region formed by the bend in the helix of one monomer of this structure were carried out for many diverse functional groups. Six critical interaction sites were identified. The Protein Data Bank was searched for backbone templates to use in the subsequent design process by matching to these sites. A 14 residue helix expected to bind to the d-isomer of the target structure was selected as the template. Over 200 000 mutant sequences of this peptide were generated based on the MCSS results. A secondary structure prediction algorithm was used to screen all sequences, and in general only those that were predicted to be highly helical were retained. Approximately 100 of these 14-mers were model built as d-peptides and docked with the l-isomer of the target monomer. Based on calculated interaction energies, predicted helicity, and intrahelical salt bridge patterns, a small number of peptides were selected as the most promising candidates. The ligand design approach presented here is the computational analogue of mirror image phage display. The results have been used to characterize the interactions responsible for formation of this model anti-parallel coiled coil and to suggest potential ligands to disrupt it.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
</region>
<settlement><li>Cambridge (Massachusetts)</li>
</settlement>
<orgName><li>Université Harvard</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Elkin, Carl D" sort="Elkin, Carl D" uniqKey="Elkin C" first="Carl D." last="Elkin">Carl D. Elkin</name>
</region>
<name sortKey="Hogle, James M" sort="Hogle, James M" uniqKey="Hogle J" first="James M." last="Hogle">James M. Hogle</name>
<name sortKey="Joseph Mccarthy, Diane" sort="Joseph Mccarthy, Diane" uniqKey="Joseph Mccarthy D" first="Diane" last="Joseph-Mccarthy">Diane Joseph-Mccarthy</name>
<name sortKey="Zuccola, Harmon J" sort="Zuccola, Harmon J" uniqKey="Zuccola H" first="Harmon J." last="Zuccola">Harmon J. Zuccola</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003752 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003752 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Main |étape= Exploration |type= RBID |clé= ISTEX:C489559D93B9D694AB570E69C703A2A254D4A5B2 |texte= Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |