{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:49:52Z","timestamp":1786470592366,"version":"build-2736575974"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,8,27]]},"abstract":"<jats:p>Allosteric regulation plays an important role in a myriad of biomacromolecular processes. Specifically, in a protein, the process of allostery refers to the transmission of a local perturbation, such as ligand binding, to a distant site. Decades after the discovery of this phenomenon, models built on static images of proteins are being reconsidered with the knowledge that protein dynamics plays an important role in its function. Molecular dynamics simulations are a valuable tool for studying complex biomolecular systems, providing an atomistic description of their structure and dynamics. Unfortunately, their predictive power has been limited by the complexity of the biomolecule free-energy surface and by the length of the allosteric timescale (in the order of milliseconds). In this work, we are able to probe the origins of the allosteric changes that transcription factor mixed lineage leukemia (MLL) causes to the interactions of KIX domain of CREB-binding protein (CBP) with phosphorylated kinase inducible domain (pKID), by combing all-atom molecular dynamics with enhanced sampling methods recently developed in our group. We discuss our results in relation to previous NMR studies. We also develop a general simulations protocol to study allosteric phenomena and many other biological processes that occur in the micro\/milliseconds timescale.<\/jats:p>","DOI":"10.1073\/pnas.1313548110","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T21:53:00Z","timestamp":1376344380000},"page":"14237-14242","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":60,"title":["The allosteric communication pathways in KIX domain of CBP"],"prefix":"10.1073","volume":"110","author":[{"given":"Ferruccio","family":"Palazzesi","sequence":"first","affiliation":[{"name":"Department of Chemistry and Applied Biosciences, Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich, CH-8093 Zurich, Switzerland;"},{"name":"Facolt\u00e0 di Informatica, Istituto di Scienze Computazionali, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Barducci","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences, Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich, CH-8093 Zurich, Switzerland;"},{"name":"Facolt\u00e0 di Informatica, Istituto di Scienze Computazionali, Universit\u00e0 della Svizzera Italiana, 6900 Lugano, Switzerland;"},{"name":"Laboratoire de Biophysique Statistique, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Tollinger","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, 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