{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:56:34Z","timestamp":1789854994024,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T00:00:00Z","timestamp":1554422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009469","name":"Conseil R\u00e9gional du Centre-Val de Loire","doi-asserted-by":"publisher","award":["APR-IR 2016"],"award-info":[{"award-number":["APR-IR 2016"]}],"id":[{"id":"10.13039\/501100009469","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR KISS ANR-15-CE20-0015"],"award-info":[{"award-number":["ANR KISS ANR-15-CE20-0015"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009895","name":"Canc\u00e9rop\u00f4le Grand Ouest","doi-asserted-by":"publisher","award":["REPiCGO"],"award-info":[{"award-number":["REPiCGO"]}],"id":[{"id":"10.13039\/501100009895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Peptide\u2013protein interactions are corner-stones of living functions involved in essential mechanisms, such as cell signaling. Given the difficulty of obtaining direct experimental structural biology data, prediction of those interactions is of crucial interest for the rational development of new drugs, notably to fight diseases, such as cancer or Alzheimer\u2019s disease. Because of the high flexibility of natural unconstrained linear peptides, prediction of their binding mode in a protein cavity remains challenging. Several theoretical approaches have been developed in the last decade to address this issue. Nevertheless, improvements are needed, such as the conformation prediction of peptide side-chains, which are dependent on peptide length and flexibility. Here, we present a novel in silico method, Iterative Residue Docking and Linking (IRDL), to efficiently predict peptide\u2013protein interactions. In order to reduce the conformational space, this innovative method splits peptides into several short segments. Then, it uses the performance of intramolecular covalent docking to rebuild, sequentially, the complete peptide in the active site of its protein target. Once the peptide is constructed, a rescoring step is applied in order to correctly rank all IRDL solutions. Applied on a set of 11 crystallized peptide\u2013protein complexes, the IRDL method shows promising results, since it is able to retrieve experimental binding conformations with a Root Mean Square Deviation (RMSD) below 2 \u00c5 in the top five ranked solutions. For some complexes, IRDL method outperforms two other docking protocols evaluated in this study. Hence, IRDL is a new tool that could be used in drug design projects to predict peptide\u2013protein interactions.<\/jats:p>","DOI":"10.3390\/molecules24071351","type":"journal-article","created":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T11:36:01Z","timestamp":1554464161000},"page":"1351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In Silico Peptide Ligation: Iterative Residue Docking and Linking as a New Approach to Predict Protein-Peptide Interactions"],"prefix":"10.3390","volume":"24","author":[{"given":"Julien","family":"Diharce","sequence":"first","affiliation":[{"name":"Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Universit\u00e9 d\u2019Orl\u00e9ans 7311, Universit\u00e9 d\u2019Orl\u00e9ans BP 6759, 45067 Orl\u00e9ans Cedex 2, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micka\u00ebl","family":"Cueto","sequence":"additional","affiliation":[{"name":"Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Universit\u00e9 d\u2019Orl\u00e9ans 7311, Universit\u00e9 d\u2019Orl\u00e9ans BP 6759, 45067 Orl\u00e9ans Cedex 2, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3472-2477","authenticated-orcid":false,"given":"Massimiliano","family":"Beltramo","sequence":"additional","affiliation":[{"name":"UMR Physiologie de la Reproduction et des Comportements (INRA, UMR85; CNRS, UMR7247; Universit\u00e9 de Tours; IFCE), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Aucagne","sequence":"additional","affiliation":[{"name":"Centre de Biophysique Mol\u00e9culaire (CNRS UPR4301), Rue Charles Sadron, F-45071 Orl\u00e9ans Cedex 2, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-138X","authenticated-orcid":false,"given":"Pascal","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Universit\u00e9 d\u2019Orl\u00e9ans 7311, Universit\u00e9 d\u2019Orl\u00e9ans BP 6759, 45067 Orl\u00e9ans Cedex 2, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1126\/science.1083653","article-title":"Assembly of Cell Regulatory Systems through Protein Interaction Domains","volume":"300","author":"Pawson","year":"2003","journal-title":"Science"},{"key":"ref_2","unstructured":"Manson, L.A. 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