{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:14:38Z","timestamp":1789193678923,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/I\/15\/1\/501847"],"award-info":[{"award-number":["IA\/I\/15\/1\/501847"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2025,4,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Disease\u2010related protein\u2010protein interactions are important molecular targets for drug discovery campaigns. The dynamics of a disordered loop, which are commonly found in the receptor binding domain of many proteins, often plays a decisive role during protein\u2010protein or protein\u2010small molecule binding events. One notable example is the interactions between two proteins from <jats:italic>Plasmodium falciparum<\/jats:italic>, <jats:italic>Pf<\/jats:italic>AMA1\u2010<jats:italic>Pf<\/jats:italic>RON2, which are crucial for the malaria parasite's invasion into human red blood cells. A thorough understanding of the interactions between these macromolecular binding partners is important for designing better therapeutics against this ancient disease. The available crystal structures of the <jats:italic>Pf<\/jats:italic>AMA1\u2010<jats:italic>Pf<\/jats:italic>RON2 complex show insufficient electron density, making it challenging to fully understand the molecular\u2010level association of the domain II (DII) loop with the <jats:italic>Pf<\/jats:italic>RON2. To address this, we have computationally simulated the dynamics and free energetics of DII loop closing processes, identifying a set of key amino acid residues in the <jats:italic>Pf<\/jats:italic>RON2 helix that are essential for binding. The subsequent experimental validation of the relative importance of residues in context provides a comprehensive understanding of the molecular recognition event between <jats:italic>Pf<\/jats:italic>AMA1 and <jats:italic>Pf<\/jats:italic>RON2, specifically in the post\u2010binding stage. This insight could potentially open up new avenues to drug discovery against malaria.<\/jats:p>","DOI":"10.1002\/cbic.202400894","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:26:05Z","timestamp":1741724765000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Cryptic Loop that Modulates Protein\u2010Protein Interaction: Implications in <i>Pf<\/i>AMA1\u2010<i>Pf<\/i>RON2 Late\u2010stage Binding Event"],"prefix":"10.1002","volume":"26","author":[{"given":"Suman","family":"Sinha","sequence":"first","affiliation":[{"name":"Tata Institute of Fundamental Research Hyderabad  36\/p Gopanpally Hyderabad Telangana 500046 India"},{"name":"Present Address: Institute of Pharmaceutical Research GLA University  Mathura 281406"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anamika","family":"Biswas","sequence":"additional","affiliation":[{"name":"Tata Institute of Fundamental Research Hyderabad  36\/p Gopanpally Hyderabad Telangana 500046 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Sahil","sequence":"additional","affiliation":[{"name":"Tata Institute of Fundamental Research Hyderabad  36\/p Gopanpally Hyderabad Telangana 500046 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagannath","family":"Mondal","sequence":"additional","affiliation":[{"name":"Tata Institute of Fundamental Research Hyderabad  36\/p Gopanpally Hyderabad Telangana 500046 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-1378","authenticated-orcid":false,"given":"Kalyaneswar","family":"Mandal","sequence":"additional","affiliation":[{"name":"Tata Institute of Fundamental Research Hyderabad  36\/p Gopanpally Hyderabad Telangana 500046 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00623"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1580"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019302"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3839"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.05.020"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp0716583"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501637102"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110303108"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144764"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.092619"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.080770"},{"key":"e_1_2_10_12_1","unstructured":"\u00a0"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjsbx.2024.100110"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi5012089"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm500390g"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002755"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800802"},{"key":"e_1_2_10_18_1","volume":"26","author":"Biswas A.","year":"2021","journal-title":"Biochem. 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