<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-02145507</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-24T21:38:54+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">CovaDOTS: In Silico Chemistry-Driven Tool to Design Covalent Inhibitors Using a Linking Strategy</title>
            <title xml:lang="eng">CovaDOTS: In Silico Chemistry-Driven Tool to Design Covalent Inhibitors Using a Linking Strategy.</title>
            <author role="aut">
              <persName>
                <forename type="first">Laurent</forename>
                <surname>Hoffer</surname>
              </persName>
              <idno type="halauthorid">741700-0</idno>
              <affiliation ref="#struct-179570"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Magali</forename>
                <surname>Saez-Ayala</surname>
              </persName>
              <idno type="halauthorid">1109188-0</idno>
              <affiliation ref="#struct-179570"/>
              <affiliation ref="#struct-198056"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Dragos</forename>
                <surname>Horvath</surname>
              </persName>
              <email type="md5">4358c9c20dee546e17d652ddaab23e07</email>
              <email type="domain">unistra.fr</email>
              <idno type="idhal" notation="string">dragos-horvath</idno>
              <idno type="idhal" notation="numeric">178284</idno>
              <idno type="halauthorid" notation="string">45017-178284</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/W-9789-2018</idno>
              <idno type="ORCID">https://orcid.org/0000-0003-0173-5714</idno>
              <idno type="IDREF">https://www.idref.fr/108942368</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/W-9789-2018</idno>
              <affiliation ref="#struct-411607"/>
              <affiliation ref="#struct-199013"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Alexandre</forename>
                <surname>Varnek</surname>
              </persName>
              <email type="md5">63c1f6fb646726b9dbf820624839dd0c</email>
              <email type="domain">chimie.u-strasbg.fr</email>
              <idno type="idhal" notation="numeric">797954</idno>
              <idno type="halauthorid" notation="string">125727-797954</idno>
              <idno type="ORCID">https://orcid.org/0000-0003-1886-925X</idno>
              <idno type="IDREF">https://www.idref.fr/124416993</idno>
              <idno type="GOOGLE SCHOLAR">https://scholar.google.fr/citations?user=hcMM9qYAAAAJ</idno>
              <idno type="VIAF">https://viaf.org/viaf/53685625</idno>
              <idno type="ISNI">http://isni.org/isni/0000000116443453</idno>
              <affiliation ref="#struct-411607"/>
              <affiliation ref="#struct-199013"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Xavier</forename>
                <surname>Morelli</surname>
              </persName>
              <email type="md5">334887f26f58085fbd2c4ba174ba78ff</email>
              <email type="domain">ifr88.cnrs-mrs.fr</email>
              <idno type="idhal" notation="string">xavier-morelli</idno>
              <idno type="idhal" notation="numeric">8470</idno>
              <idno type="halauthorid" notation="string">8995-8470</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/A-9218-2016</idno>
              <idno type="ORCID">https://orcid.org/0000-0001-8101-7901</idno>
              <idno type="IDREF">https://www.idref.fr/155010239</idno>
              <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/A-9218-2016</idno>
              <affiliation ref="#struct-179570"/>
              <affiliation ref="#struct-198056"/>
              <affiliation ref="#struct-441569"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Philippe</forename>
                <surname>Roche</surname>
              </persName>
              <idno type="halauthorid">29849-0</idno>
              <affiliation ref="#struct-179570"/>
              <affiliation ref="#struct-198056"/>
              <affiliation ref="#struct-441569"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Philippe</forename>
                <surname>ROCHE</surname>
              </persName>
              <email type="md5">05bd4e90416d28fcf899ae9ce3c64699</email>
              <email type="domain">inserm.fr</email>
            </editor>
            <funder ref="#projanr-45474"/>
            <funder ref="#projanr-52326"/>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2019-06-03 09:35:06</date>
              <date type="whenModified">2026-04-24 12:02:02</date>
              <date type="whenReleased">2024-11-13 09:53:53</date>
              <date type="whenProduced">2019-01-24</date>
              <date type="whenEndEmbargoed">2024-11-06</date>
              <ref type="file" target="https://hal.science/hal-02145507v1/document">
                <date notBefore="2024-11-06"/>
              </ref>
              <ref type="file" subtype="author" n="1" target="https://hal.science/hal-02145507v1/file/Hoffer-etal_2019_CovaDOTS.pdf" id="file-4769214-4153276">
                <date notBefore="2024-11-06"/>
              </ref>
              <ref type="externalLink" target="https://hal.archives-ouvertes.fr/hal-02145507/file/Hoffer_etal_JMedChem_2018.pdf"/>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="339179">
                <persName>
                  <forename>Philippe</forename>
                  <surname>ROCHE</surname>
                </persName>
                <email type="md5">05bd4e90416d28fcf899ae9ce3c64699</email>
                <email type="domain">inserm.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-02145507</idno>
            <idno type="halUri">https://hal.science/hal-02145507</idno>
            <idno type="halBibtex">hoffer:hal-02145507</idno>
            <idno type="halRefHtml">&lt;i&gt;Journal of Chemical Information and Modeling&lt;/i&gt;, 2019, 59 (4), pp.1472-1485. &lt;a target="_blank" href="https://dx.doi.org/10.1021/acs.jcim.8b00960"&gt;&amp;#x27E8;10.1021/acs.jcim.8b00960&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Journal of Chemical Information and Modeling, 2019, 59 (4), pp.1472-1485. &amp;#x27E8;10.1021/acs.jcim.8b00960&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://about.hal.science/hal-authorisation-v1/">HAL Authorization<ref corresp="#file-4769214-4153276"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="UNIV-AMU">Aix Marseille Université</idno>
            <idno type="stamp" n="UNIV-STRASBG">Université de Strasbourg</idno>
            <idno type="stamp" n="INC-CNRS">Institut de Chimie du CNRS</idno>
            <idno type="stamp" n="SITE-ALSACE">Archive ouverte du site Alsace</idno>
            <idno type="stamp" n="CRCM">Centre de Recherche en Cancérologie de Marseille</idno>
            <idno type="stamp" n="TEST-HALCNRS">Collection test HAL CNRS</idno>
            <idno type="stamp" n="ANR">ANR</idno>
            <idno type="stamp" n="UNIVOAK">UNIVOAK</idno>
            <idno type="stamp" n="CMC">Chimie de la matière complexe</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">CovaDOTS: In Silico Chemistry-Driven Tool to Design Covalent Inhibitors Using a Linking Strategy</title>
                <title xml:lang="eng">CovaDOTS: In Silico Chemistry-Driven Tool to Design Covalent Inhibitors Using a Linking Strategy.</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Laurent</forename>
                    <surname>Hoffer</surname>
                  </persName>
                  <idno type="halauthorid">741700-0</idno>
                  <affiliation ref="#struct-179570"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Magali</forename>
                    <surname>Saez-Ayala</surname>
                  </persName>
                  <idno type="halauthorid">1109188-0</idno>
                  <affiliation ref="#struct-179570"/>
                  <affiliation ref="#struct-198056"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Dragos</forename>
                    <surname>Horvath</surname>
                  </persName>
                  <email type="md5">4358c9c20dee546e17d652ddaab23e07</email>
                  <email type="domain">unistra.fr</email>
                  <idno type="idhal" notation="string">dragos-horvath</idno>
                  <idno type="idhal" notation="numeric">178284</idno>
                  <idno type="halauthorid" notation="string">45017-178284</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/W-9789-2018</idno>
                  <idno type="ORCID">https://orcid.org/0000-0003-0173-5714</idno>
                  <idno type="IDREF">https://www.idref.fr/108942368</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/W-9789-2018</idno>
                  <affiliation ref="#struct-411607"/>
                  <affiliation ref="#struct-199013"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Alexandre</forename>
                    <surname>Varnek</surname>
                  </persName>
                  <email type="md5">63c1f6fb646726b9dbf820624839dd0c</email>
                  <email type="domain">chimie.u-strasbg.fr</email>
                  <idno type="idhal" notation="numeric">797954</idno>
                  <idno type="halauthorid" notation="string">125727-797954</idno>
                  <idno type="ORCID">https://orcid.org/0000-0003-1886-925X</idno>
                  <idno type="IDREF">https://www.idref.fr/124416993</idno>
                  <idno type="GOOGLE SCHOLAR">https://scholar.google.fr/citations?user=hcMM9qYAAAAJ</idno>
                  <idno type="VIAF">https://viaf.org/viaf/53685625</idno>
                  <idno type="ISNI">http://isni.org/isni/0000000116443453</idno>
                  <affiliation ref="#struct-411607"/>
                  <affiliation ref="#struct-199013"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Xavier</forename>
                    <surname>Morelli</surname>
                  </persName>
                  <email type="md5">334887f26f58085fbd2c4ba174ba78ff</email>
                  <email type="domain">ifr88.cnrs-mrs.fr</email>
                  <idno type="idhal" notation="string">xavier-morelli</idno>
                  <idno type="idhal" notation="numeric">8470</idno>
                  <idno type="halauthorid" notation="string">8995-8470</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/A-9218-2016</idno>
                  <idno type="ORCID">https://orcid.org/0000-0001-8101-7901</idno>
                  <idno type="IDREF">https://www.idref.fr/155010239</idno>
                  <idno type="RESEARCHERID">http://www.researcherid.com/rid/http://www.researcherid.com/rid/A-9218-2016</idno>
                  <affiliation ref="#struct-179570"/>
                  <affiliation ref="#struct-198056"/>
                  <affiliation ref="#struct-441569"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Philippe</forename>
                    <surname>Roche</surname>
                  </persName>
                  <idno type="halauthorid">29849-0</idno>
                  <affiliation ref="#struct-179570"/>
                  <affiliation ref="#struct-198056"/>
                  <affiliation ref="#struct-441569"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">21974</idno>
                <idno type="issn">1549-9596</idno>
                <idno type="eissn">1549-960X</idno>
                <title level="j">Journal of Chemical Information and Modeling</title>
                <imprint>
                  <publisher>American Chemical Society</publisher>
                  <biblScope unit="volume">59</biblScope>
                  <biblScope unit="issue">4</biblScope>
                  <biblScope unit="pp">1472-1485</biblScope>
                  <date type="datePub">2019-01-24</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1021/acs.jcim.8b00960</idno>
              <idno type="pubmed">30908019</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <classCode scheme="halDomain" n="sdv.bibs">Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>We recently reported an integrated fragment-based optimization strategy called DOTS (Diversity Oriented Target-focused Synthesis) that combines automated virtual screening (VS) with semirobotized organic synthesis coupled to in vitro evaluation. The molecular modeling part consists of hit-to-lead chemistry, based on the growing paradigm. Here, we have extended the applicability of the DOTS strategy by adding new functionalities, allowing a generic chemistry-driven linking approach with a particular emphasis on covalent drugs. Indeed, the covalent mode of action can be described as a specific case of linking, where suitable linkers are sought to fuse a bound organic compound with a nucleophilic protein side chain. The proof of concept is established using three retrospective study cases in which known noncovalent inhibitors have been converted to covalent inhibitors. Our method is able to automatically design reference covalent inhibitors (and/or analogs) from an initial activated substructure and predict their binding mode. More importantly, the reference compounds are ranked high among several hundred putative adducts, demonstrating the utility of the approach to design covalent inhibitors.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-179570" status="VALID">
          <idno type="RNSR">201220152G</idno>
          <idno type="ROR">0494jpz02</idno>
          <orgName>Centre de Recherche en Cancérologie de Marseille</orgName>
          <orgName type="acronym">CRCM</orgName>
          <date type="start">2012</date>
          <desc>
            <address>
              <addrLine>27 bd Leï Roure, BP 30005913273 Marseille Cedex 09</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://crcm.marseille.inserm.fr/spip.php?article314</ref>
          </desc>
          <listRelation>
            <relation name="UM105" active="#struct-198056" type="direct"/>
            <relation name="UMR7258" active="#struct-301325" type="direct"/>
            <relation active="#struct-301051" type="indirect"/>
            <relation name="U1068" active="#struct-303623" type="direct"/>
            <relation name="UMR7258" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-198056" status="VALID">
          <idno type="IdRef">15863621X</idno>
          <idno type="ISNI">0000 0001 2176 4817</idno>
          <idno type="ROR">https://ror.org/035xkbk20</idno>
          <orgName>Aix Marseille Université</orgName>
          <orgName type="acronym">AMU</orgName>
          <date type="start">2012-01-01</date>
          <desc>
            <address>
              <addrLine>Aix-Marseille UniversitéJardins du Pharo58 Boulevard Charles Livon13284 Marseille cedex 7</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.univ-amu.fr/</ref>
          </desc>
        </org>
        <org type="researchteam" xml:id="struct-411607" status="VALID">
          <orgName>Laboratoire de Chémoinformatique</orgName>
          <date type="start">2013-01-01</date>
          <desc>
            <address>
              <addrLine>Institut Le Bel, 4 rue Blaise Pascal - CS 90032 67081 Strasbourg Cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://complex-matter.unistra.fr/equipes-de-recherche/laboratoire-de-chemoinformatique/home/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-403339" type="direct"/>
            <relation active="#struct-199013" type="indirect"/>
            <relation active="#struct-341038" type="indirect"/>
            <relation name="UMR7140" active="#struct-441569" type="indirect"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-199013" status="VALID">
          <idno type="IdRef">131056549</idno>
          <idno type="ROR">https://ror.org/00pg6eq24</idno>
          <orgName>Université de Strasbourg</orgName>
          <orgName type="acronym">UNISTRA</orgName>
          <desc>
            <address>
              <addrLine>4 rue Blaise Pascal - CS 90032 - 67081 Strasbourg cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.unistra.fr/</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-301325" status="VALID">
          <idno type="ROR">https://ror.org/04s3t1g37</idno>
          <orgName>Institut Paoli-Calmettes</orgName>
          <orgName type="acronym">IPC</orgName>
          <desc>
            <address>
              <addrLine>232 Boulevard de Sainte-Marguerite13009 Marseille</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.institutpaolicalmettes.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-301051" type="direct"/>
          </listRelation>
        </org>
        <org type="regroupinstitution" xml:id="struct-301051" status="VALID">
          <orgName>Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)</orgName>
          <desc>
            <address>
              <country key="FR"/>
            </address>
          </desc>
        </org>
        <org type="institution" xml:id="struct-303623" status="VALID">
          <idno type="IdRef">026388278</idno>
          <idno type="ROR">https://ror.org/02vjkv261</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>
            <address>
              <addrLine>101, rue de Tolbiac, 75013 Paris</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
        <org type="laboratory" xml:id="struct-403339" status="VALID">
          <idno type="IdRef">157547027</idno>
          <idno type="ISNI">0000000403671184</idno>
          <idno type="RNSR">200312525F</idno>
          <idno type="ROR">https://ror.org/01cgac405</idno>
          <idno type="Wikidata">Q51781651</idno>
          <orgName>Chimie de la matière complexe</orgName>
          <orgName type="acronym">CMC</orgName>
          <date type="start">2013-01-01</date>
          <desc>
            <address>
              <addrLine>Institut Le Bel - 4, rue Blaise Pascal - 67070 STRASBOURG CEDEX</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://complex-matter.unistra.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-199013" type="direct"/>
            <relation active="#struct-341038" type="direct"/>
            <relation name="UMR7140" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-341038" status="VALID">
          <idno type="IdRef">232435103</idno>
          <idno type="ISNI">000000010626358X</idno>
          <idno type="ROR">https://ror.org/02cte4b68</idno>
          <orgName>Institut de Chimie - CNRS Chimie</orgName>
          <orgName type="acronym">INC-CNRS</orgName>
          <date type="start">2009-10-01</date>
          <desc>
            <address>
              <addrLine>CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE3 rue Michel-Ange75794 PARIS CEDEX 16 - France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.cnrs.fr/inc</ref>
          </desc>
        </org>
      </listOrg>
      <listOrg type="projects">
        <org type="anrProject" xml:id="projanr-45474" status="VALID">
          <idno type="anr">ANR-15-CE18-0023</idno>
          <orgName>PPI-Chem</orgName>
          <desc>Développement de stratégies innovantes ciblant la modulation spécifique de complexes protéine-proteine</desc>
          <date type="start">2015</date>
        </org>
        <org type="anrProject" xml:id="projanr-52326" status="VALID">
          <idno type="anr">ANR-20-CE18-0025</idno>
          <orgName>Cov-H2L</orgName>
          <desc>Développement d'une méthodologie accélérant l'identification et l'optimisation de hits covalents</desc>
          <date type="start">2020</date>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>