Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization.
Identifieur interne : 000077 ( Ncbi/Merge ); précédent : 000076; suivant : 000078Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization.
Auteurs : C D Elkin [États-Unis] ; H J Zuccola ; J M Hogle ; D. Joseph-MccarthySource :
- Journal of computer-aided molecular design [ 0920-654X ] ; 2000.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- 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
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.
DOI: 10.1023/a:1008146015629
PubMed: 11131965
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002604
- to stream PubMed, to step Curation: 002604
- to stream PubMed, to step Checkpoint: 002451
Links to Exploration step
pubmed:11131965Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization.</title><author><name sortKey="Elkin, C D" sort="Elkin, C D" uniqKey="Elkin C" first="C D" last="Elkin">C D Elkin</name><affiliation wicri:level="4"><nlm:affiliation>Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Zuccola, H J" sort="Zuccola, H J" uniqKey="Zuccola H" first="H J" last="Zuccola">H J Zuccola</name></author><author><name sortKey="Hogle, J M" sort="Hogle, J M" uniqKey="Hogle J" first="J M" last="Hogle">J M Hogle</name></author><author><name sortKey="Joseph Mccarthy, D" sort="Joseph Mccarthy, D" uniqKey="Joseph Mccarthy D" first="D" last="Joseph-Mccarthy">D. Joseph-Mccarthy</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:11131965</idno><idno type="pmid">11131965</idno><idno type="doi">10.1023/a:1008146015629</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></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization.</title><author><name sortKey="Elkin, C D" sort="Elkin, C D" uniqKey="Elkin C" first="C D" last="Elkin">C D Elkin</name><affiliation wicri:level="4"><nlm:affiliation>Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Zuccola, H J" sort="Zuccola, H J" uniqKey="Zuccola H" first="H J" last="Zuccola">H J Zuccola</name></author><author><name sortKey="Hogle, J M" sort="Hogle, J M" uniqKey="Hogle J" first="J M" last="Hogle">J M Hogle</name></author><author><name sortKey="Joseph Mccarthy, D" sort="Joseph Mccarthy, D" uniqKey="Joseph Mccarthy D" first="D" last="Joseph-Mccarthy">D. Joseph-Mccarthy</name></author></analytic><series><title level="j">Journal of computer-aided molecular design</title><idno type="ISSN">0920-654X</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></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></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></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11131965</PMID><DateCompleted><Year>2001</Year><Month>02</Month><Day>15</Day></DateCompleted><DateRevised><Year>2019</Year><Month>11</Month><Day>04</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0920-654X</ISSN><JournalIssue CitedMedium="Print"><Volume>14</Volume><Issue>8</Issue><PubDate><Year>2000</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Journal of computer-aided molecular design</Title><ISOAbbreviation>J. Comput. Aided Mol. Des.</ISOAbbreviation></Journal><ArticleTitle>Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization.</ArticleTitle><Pagination><MedlinePgn>705-18</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Elkin</LastName><ForeName>C D</ForeName><Initials>CD</Initials><AffiliationInfo><Affiliation>Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02139, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zuccola</LastName><ForeName>H J</ForeName><Initials>HJ</Initials></Author><Author ValidYN="Y"><LastName>Hogle</LastName><ForeName>J M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Joseph-McCarthy</LastName><ForeName>D</ForeName><Initials>D</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>AI32480</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Comput Aided Mol Des</MedlineTA><NlmUniqueID>8710425</NlmUniqueID><ISSNLinking>0920-654X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018963">Hepatitis Antigens</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000465" MajorTopicYN="N">Algorithms</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003628" MajorTopicYN="N">Database Management Systems</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019281" MajorTopicYN="N">Dimerization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018963" MajorTopicYN="N">Hepatitis Antigens</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003698" MajorTopicYN="N">Hepatitis Delta Virus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011487" MajorTopicYN="N">Protein Conformation</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>1</Month><Day>11</Day><Hour>19</Hour><Minute>15</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>3</Month><Day>3</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>1</Month><Day>11</Day><Hour>19</Hour><Minute>15</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11131965</ArticleId><ArticleId IdType="doi">10.1023/a:1008146015629</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10537-41</Citation><ArticleIdList><ArticleId IdType="pubmed">1438243</ArticleId></ArticleIdList></Reference><Reference><Citation>J Mol Biol. 1987 Feb 20;193(4):775-91</Citation><ArticleIdList><ArticleId IdType="pubmed">2441069</ArticleId></ArticleIdList></Reference><Reference><Citation>Proteins. 1997 Sep;29(1):32-58</Citation><ArticleIdList><ArticleId IdType="pubmed">9294865</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1996 Mar 29;271(5257):1854-7</Citation><ArticleIdList><ArticleId IdType="pubmed">8596952</ArticleId></ArticleIdList></Reference><Reference><Citation>Proteins. 1994 Jul;19(3):199-221</Citation><ArticleIdList><ArticleId IdType="pubmed">7937734</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1992 Nov;66(11):6641-8</Citation><ArticleIdList><ArticleId IdType="pubmed">1404608</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):560-6</Citation><ArticleIdList><ArticleId IdType="pubmed">15299844</ArticleId></ArticleIdList></Reference><Reference><Citation>Proteins. 1991;11(1):29-34</Citation><ArticleIdList><ArticleId IdType="pubmed">1961699</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 1987 Sep 25;262(27):13155-62</Citation><ArticleIdList><ArticleId IdType="pubmed">2443489</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):382-6</Citation><ArticleIdList><ArticleId IdType="pubmed">7831295</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1990 Oct;64(10):5066-9</Citation><ArticleIdList><ArticleId IdType="pubmed">2398535</ArticleId></ArticleIdList></Reference><Reference><Citation>Proteins. 1995 Dec;23(4):472-90</Citation><ArticleIdList><ArticleId IdType="pubmed">8749844</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1993 Jan;67(1):446-54</Citation><ArticleIdList><ArticleId IdType="pubmed">7677957</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1995 Jun;69(6):3771-7</Citation><ArticleIdList><ArticleId IdType="pubmed">7538176</ArticleId></ArticleIdList></Reference><Reference><Citation>Protein Sci. 1995 Feb;4(2):275-85</Citation><ArticleIdList><ArticleId IdType="pubmed">7757016</ArticleId></ArticleIdList></Reference><Reference><Citation>J Phys Chem B. 1998 Apr 30;102(18):3586-616</Citation><ArticleIdList><ArticleId IdType="pubmed">24889800</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9765-9</Citation><ArticleIdList><ArticleId IdType="pubmed">7937888</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1992 Jun 5;256(5062):1445-8</Citation><ArticleIdList><ArticleId IdType="pubmed">1604320</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Chem. 1993 Jul 23;36(15):2142-67</Citation><ArticleIdList><ArticleId IdType="pubmed">8340918</ArticleId></ArticleIdList></Reference><Reference><Citation>Structure. 1998 Jul 15;6(7):821-30</Citation><ArticleIdList><ArticleId IdType="pubmed">9687364</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1987 Dec;84(24):8898-902</Citation><ArticleIdList><ArticleId IdType="pubmed">3122208</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Chem. 1995 Jan 20;38(2):305-17</Citation><ArticleIdList><ArticleId IdType="pubmed">7830273</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochemistry. 1974 Jan 15;13(2):211-22</Citation><ArticleIdList><ArticleId IdType="pubmed">4358939</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9770-4</Citation><ArticleIdList><ArticleId IdType="pubmed">7937889</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Struct Biol. 1994 Oct;1(10):735-43</Citation><ArticleIdList><ArticleId IdType="pubmed">7634078</ArticleId></ArticleIdList></Reference><Reference><Citation>Protein Sci. 1998 Sep;7(9):1898-914</Citation><ArticleIdList><ArticleId IdType="pubmed">9761471</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6349-53</Citation><ArticleIdList><ArticleId IdType="pubmed">7603994</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><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><noCountry><name sortKey="Hogle, J M" sort="Hogle, J M" uniqKey="Hogle J" first="J M" last="Hogle">J M Hogle</name><name sortKey="Joseph Mccarthy, D" sort="Joseph Mccarthy, D" uniqKey="Joseph Mccarthy D" first="D" last="Joseph-Mccarthy">D. Joseph-Mccarthy</name><name sortKey="Zuccola, H J" sort="Zuccola, H J" uniqKey="Zuccola H" first="H J" last="Zuccola">H J Zuccola</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Elkin, C D" sort="Elkin, C D" uniqKey="Elkin C" first="C D" last="Elkin">C D Elkin</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000077 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000077 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= pubmed:11131965
|texte= Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:11131965" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |