<?xml version="1.0" encoding="utf-8"?>
<export-example>
  <doc>
    <id>9606</id>
    <completedYear/>
    <publishedYear>2024</publishedYear>
    <thesisYearAccepted/>
    <language>eng</language>
    <pageFirst>428</pageFirst>
    <pageLast>457</pageLast>
    <pageNumber>30</pageNumber>
    <edition/>
    <issue>4</issue>
    <volume>20</volume>
    <type>article</type>
    <publisherName>Springer Science and Business Media LLC</publisherName>
    <publisherPlace/>
    <creatingCorporation/>
    <contributingCorporation/>
    <belongsToBibliography>0</belongsToBibliography>
    <completedDate>2024-03-11</completedDate>
    <publishedDate>2024-03-11</publishedDate>
    <thesisDateAccepted>--</thesisDateAccepted>
    <title language="eng">AI-guided pipeline for protein–protein interaction drug discovery identifies a SARS-CoV-2 inhibitor</title>
    <abstract language="eng">Protein–protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays or AlphaFold-Multimer predictions. Using the quantitative assay LuTHy together with our machine learning algorithm, we identified high-confidence interactions among SARS-CoV-2 proteins for which we predicted three-dimensional structures using AlphaFold-Multimer. We employed VirtualFlow to target the contact interface of the NSP10-NSP16 SARS-CoV-2 methyltransferase complex by ultra-large virtual drug screening. Thereby, we identified a compound that binds to NSP10 and inhibits its interaction with NSP16, while also disrupting the methyltransferase activity of the complex, and SARS-CoV-2 replication. Overall, this pipeline will help to prioritize PPI targets to accelerate the discovery of early-stage drug candidates targeting protein complexes and pathways.</abstract>
    <parentTitle language="eng">Molecular Systems Biology</parentTitle>
    <identifier type="doi">https://doi.org/10.1038/s44320-024-00019-8</identifier>
    <identifier type="issn">1744-4292</identifier>
    <enrichment key="opus_doi_flag">true</enrichment>
    <enrichment key="opus_doi_json">x</enrichment>
    <enrichment key="opus_crossrefDocumentType">journal-article</enrichment>
    <enrichment key="opus_crossrefLicence">https://creativecommons.org/licenses/by/4.0</enrichment>
    <enrichment key="opus_import_origin">crossref</enrichment>
    <enrichment key="opus_doiImportPopulated">SubjectUncontrolled_1,SubjectUncontrolled_2,SubjectUncontrolled_3,SubjectUncontrolled_4,SubjectUncontrolled_5,SubjectUncontrolled_6,PersonAuthorFirstName_1,PersonAuthorLastName_1,PersonAuthorIdentifierOrcid_1,PersonAuthorFirstName_2,PersonAuthorLastName_2,PersonAuthorIdentifierOrcid_2,PersonAuthorFirstName_3,PersonAuthorLastName_3,PersonAuthorIdentifierOrcid_3,PersonAuthorFirstName_4,PersonAuthorLastName_4,PersonAuthorIdentifierOrcid_4,PersonAuthorFirstName_5,PersonAuthorLastName_5,PersonAuthorFirstName_6,PersonAuthorLastName_6,PersonAuthorIdentifierOrcid_6,PersonAuthorFirstName_7,PersonAuthorLastName_7,PersonAuthorFirstName_8,PersonAuthorLastName_8,PersonAuthorIdentifierOrcid_8,PersonAuthorFirstName_9,PersonAuthorLastName_9,PersonAuthorFirstName_10,PersonAuthorLastName_10,PersonAuthorFirstName_11,PersonAuthorLastName_11,PersonAuthorFirstName_12,PersonAuthorLastName_12,PersonAuthorFirstName_13,PersonAuthorLastName_13,PersonAuthorFirstName_14,PersonAuthorLastName_14,PersonAuthorFirstName_15,PersonAuthorLastName_15,PersonAuthorIdentifierOrcid_15,PersonAuthorFirstName_16,PersonAuthorLastName_16,PersonAuthorIdentifierOrcid_16,PersonAuthorFirstName_17,PersonAuthorLastName_17,PersonAuthorIdentifierOrcid_17,PersonAuthorFirstName_18,PersonAuthorLastName_18,PersonAuthorFirstName_19,PersonAuthorLastName_19,PersonAuthorFirstName_20,PersonAuthorLastName_20,PersonAuthorFirstName_21,PersonAuthorLastName_21,PersonAuthorIdentifierOrcid_21,PersonAuthorFirstName_22,PersonAuthorLastName_22,PersonAuthorIdentifierOrcid_22,PersonAuthorFirstName_23,PersonAuthorLastName_23,PersonAuthorIdentifierOrcid_23,PersonAuthorFirstName_24,PersonAuthorLastName_24,PersonAuthorIdentifierOrcid_24,PersonAuthorFirstName_25,PersonAuthorLastName_25,PersonAuthorIdentifierOrcid_25,PersonAuthorFirstName_26,PersonAuthorLastName_26,PersonAuthorIdentifierOrcid_26,PersonAuthorFirstName_27,PersonAuthorLastName_27,PersonAuthorIdentifierOrcid_27,PublisherName,TitleMain_1,Language,TitleAbstract_1,TitleParent_1,PageNumber,PageFirst,PageLast,Issue,Volume,PublishedYear,IdentifierIssn,Enrichmentopus_crossrefLicence</enrichment>
    <enrichment key="PeerReviewed">yes</enrichment>
    <enrichment key="opus.source">doi-import</enrichment>
    <author>Philipp Trepte</author>
    <submitter>Christopher Secker</submitter>
    <author>Christopher Secker</author>
    <author>Julien Olivet</author>
    <author>Jeremy Blavier</author>
    <author>Simona Kostova</author>
    <author>Sibusiso B Maseko</author>
    <author>Igor Minia</author>
    <author>Eduardo Silva Ramos</author>
    <author>Patricia Cassonnet</author>
    <author>Sabrina Golusik</author>
    <author>Martina Zenkner</author>
    <author>Stephanie Beetz</author>
    <author>Mara J Liebich</author>
    <author>Nadine Scharek</author>
    <author>Anja Schütz</author>
    <author>Marcel Sperling</author>
    <author>Michael Lisurek</author>
    <author>Yang Wang</author>
    <author>Kerstin Spirohn</author>
    <author>Tong Hao</author>
    <author>Michael A Calderwood</author>
    <author>David E Hill</author>
    <author>Markus Landthaler</author>
    <author>Soon Gang Choi</author>
    <author>Jean-Claude Twizere</author>
    <author>Marc Vidal</author>
    <author>Erich E Wanker</author>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Applied Mathematics</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Computational Theory and Mathematics</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>General Agricultural and Biological Sciences</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>General Immunology and Microbiology</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>General Biochemistry, Genetics and Molecular Biology</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Information Systems</value>
    </subject>
    <collection role="institutes" number="compmol">Computational Molecular Design</collection>
    <collection role="institutes" number="scp">Supercomputing</collection>
    <collection role="institutes" number="MSoCP">Modeling and Simulation of Complex Processes</collection>
    <collection role="institutes" number="Mathematical Algorithmic Intelligence">Mathematical Algorithmic Intelligence</collection>
    <collection role="institutes" number="PaDC">Parallel and Distributed Computing</collection>
    <collection role="persons" number="secker">Secker, Christopher</collection>
    <collection role="projects" number="MathPlusAA1-19">MathPlusAA1-19</collection>
  </doc>
  <doc>
    <id>9345</id>
    <completedYear/>
    <publishedYear/>
    <thesisYearAccepted/>
    <language>eng</language>
    <pageFirst/>
    <pageLast/>
    <pageNumber/>
    <edition/>
    <issue/>
    <volume/>
    <type>article</type>
    <publisherName/>
    <publisherPlace/>
    <creatingCorporation/>
    <contributingCorporation/>
    <belongsToBibliography>0</belongsToBibliography>
    <completedDate>--</completedDate>
    <publishedDate>2023-06-14</publishedDate>
    <thesisDateAccepted>--</thesisDateAccepted>
    <title language="eng">AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor</title>
    <parentTitle language="eng">bioRxiv</parentTitle>
    <identifier type="doi">10.1101/2023.06.14.544560</identifier>
    <enrichment key="PeerReviewed">no</enrichment>
    <enrichment key="opus.source">publish</enrichment>
    <enrichment key="FulltextUrl">https://doi.org/10.1101/2023.06.14.544560</enrichment>
    <author>Philipp Trepte</author>
    <author>Christopher Secker</author>
    <author>Simona Kostova</author>
    <author>Sibusiso B. Maseko</author>
    <author>Soon Gang Choi</author>
    <author>Jeremy Blavier</author>
    <author>Igor Minia</author>
    <author>Eduardo Silva Ramos</author>
    <author>Patricia Cassonnet</author>
    <author>Sabrina Golusik</author>
    <author>Martina Zenkner</author>
    <author>Stephanie Beetz</author>
    <author>Mara J. Liebich</author>
    <author>Nadine Scharek</author>
    <author>Anja Schütz</author>
    <author>Marcel Sperling</author>
    <author>Michael Lisurek</author>
    <author>Yang Wang</author>
    <author>Kerstin Spirohn</author>
    <author>Tong Hao</author>
    <author>Michael A. Calderwood</author>
    <author>David E. Hill</author>
    <author>Markus Landthaler</author>
    <author>Julien Olivet</author>
    <author>Jean-Claude Twizere</author>
    <author>Marc Vidal</author>
    <author>Erich E. Wanker</author>
    <collection role="institutes" number="num">Numerical Mathematics</collection>
    <collection role="projects" number="no-project">no-project</collection>
    <collection role="institutes" number="MSoCP">Modeling and Simulation of Complex Processes</collection>
    <collection role="institutes" number="Mathematical Algorithmic Intelligence">Mathematical Algorithmic Intelligence</collection>
    <collection role="institutes" number="PaDC">Parallel and Distributed Computing</collection>
    <collection role="persons" number="secker">Secker, Christopher</collection>
  </doc>
</export-example>
