{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:51:19Z","timestamp":1791175879074,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_219549"],"award-info":[{"award-number":["310030_219549"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Allosteric communication is fundamental to the function of proteins, but identifying the residue\u2010level pathways through which signals travel and their directionality is still a major challenge. Here we present a multi\u2010metric information\u2010theoretic framework that identifies candidate allosteric communication pathways from a single protein crystal structure in seconds. The method combines Transfer Entropy (TE) from the Gaussian Network Model to assign a model\u2010based directional asymmetry to residue\u2010residue coupling, Mutual Information (MI) to quantify coupling strength, and Conditional Mutual Information (CMI) to detect relay residues that mediate indirect couplings. At the network level, Burton\u2013Pemantle ensemble random spanning trees provide robustness\u2010weighted betweenness centrality, differentiating persistent communication bottlenecks from occasional hubs. Kullback\u2013Leibler (KL) divergence of the magnitude of the net transfer entropy distributions quantifies network rewiring and identifies allosteric switches. We validate the framework on four experimentally characterized systems: PDZ3 of PSD\u201095, p38\u03b1 MAP kinase, KRAS WT versus the oncogenic G12D mutant, and kinesin\u20105 in ATP versus ADP bound states. Quantitative validation shows that the workflow captures previously reported hotspots and exceeds MI\u2010only and contact graph shortest\u2010path baselines on the all\u2010paths overlap metric, while performing at least as well as topology\u2010matched random controls. Computations take from ~14\u2009s for a 110\u2010residue domain to ~7\u2009min for a 350\u2010residue domain. on a standard laptop. Thus, the method can be applied systematically to large families of proteins.<\/jats:p>","DOI":"10.1002\/prot.70187","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:01:38Z","timestamp":1791172898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Information\u2010Theoretic Framework for Allosteric Communication Pathway Prediction From Protein Structure"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-0296","authenticated-orcid":false,"given":"Aysima","family":"Hacisuleyman","sequence":"first","affiliation":[{"name":"Department of Computational Biology University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-4282","authenticated-orcid":false,"given":"Dirk","family":"Fasshauer","sequence":"additional","affiliation":[{"name":"Department of Computational Biology University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"issue":"7496","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nature13001","article-title":"The Ensemble Nature of Allostery","volume":"508","author":"Motlagh H. 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