{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:46:36Z","timestamp":1792673196120,"version":"4.5.0"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"42","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["288\/20"],"award-info":[{"award-number":["288\/20"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NIH)","award":["R01EY029169"],"award-info":[{"award-number":["R01EY029169"]}]},{"name":"National Institutes of Health (NIH)","award":["R01GM112491"],"award-info":[{"award-number":["R01GM112491"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Article I introduced a motif-level framework for analyzing molecular dynamics (MD) backbone-dihedral trajectories, using structural motifs extending beyond a single residue as fundamental units of description. Here, Article II combines this motif-level representation with conventional backbone-dihedral-angle analysis to investigate conformational restructuring in protein loops. The peptide planes of the loop residues in the Rho GTPase-binding domain of plexin-B1 (RBD) serve as representative structural motifs. The two components of the combined analysis provide complementary information: conventional (\u03a8, \u03a6)-based analysis identifies local conformational changes, whereas motif-level analysis reveals which peptide planes move in concert and how the restructuring is organized. Importantly, this formulation also provides motif-specific structural, thermodynamic, and ordering properties\u2500local orientational potentials, probability distributions, order parameters, and entropy\u2500expressed in the natural orientational coordinates, (\u03b8, \u03c6), of the structural motif under consideration. Such information is inaccessible from conventional (\u03a8, \u03a6)-based analysis alone. Across the examples examined, a common picture emerges: distinct local conformational changes in protein loops can be realized through dynamically correlated motions of peptide planes within the scope of which the conventional and motif-level analyses connect residue-specific structural transitions with their collective structural, energetic, entropic, and ordering organization. This provides a common basis for analyzing several distinct mechanisms of conformational restructuring in the RBD, the RBD dimer, and the RBD\u2013GTPase Rac1 complex (RBD\u2013Rac1). The K50\u2013G51 peptide plane of the RBD undergoes canonical type-II-to-type-I \u03b2-turn crankshaft flips, whereas the corresponding transitions in RBD\u2013Rac1 are more intricate and noncanonical. Deviations from canonical helicity and their subsequent relaxation are characterized. In the RBD dimer, the analysis reveals a concerted dynamical process involving multiple peptide planes. A versatile dynamic hinge and through-space dynamical correlations are also identified. Importantly, the entropic contributions to the free energy differences associated with RBD dimerization and RBD\u2013Rac1 binding are assessed.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c03045","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:02:14Z","timestamp":1791907334000},"page":"11056-11072","source":"Crossref","is-referenced-by-count":0,"title":["Peptide-Plane Dynamics\nin Protein Loops from Microsecond\nMolecular Dynamics. II. Insights on Conformational Restructuring"],"prefix":"10.1021","volume":"130","author":[{"given":"Yaron","family":"Pshetitsky","sequence":"first","affiliation":[{"name":"Bar-Ilan University , , ,","place":["Ramat-Gan, Israel, 52900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Buck","sequence":"additional","affiliation":[{"name":"Case Western Reserve University , , , ,","place":["Cleveland, Ohio, United States, 44106-4970"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-5079","authenticated-orcid":true,"given":"Eva","family":"Meirovitch","sequence":"additional","affiliation":[{"name":"Bar-Ilan University , , ,","place":["Ramat-Gan, Israel, 52900"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"2026102207422950300_cit1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/978-1-61779-334-9_13","article-title":"Combining NMR and Molecular\nDynamics Studies for Insights into the Allostery of Small GTPase\u2013Protein\nInteractions","volume-title":"Allostery: Methods and Protocols","author":"Zhang","year":"2012"},{"key":"2026102207422950300_cit2","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1002\/pro.116","article-title":"Thermodynamic Characterization of\nTwo Homologous Protein Complexes:\nAssociations of the Semaphorin Receptor Plexin-B1 RhoGTPase Binding\nDomain with Rnd1 and Active Rac1","volume":"18","author":"Hota","year":"2009","journal-title":"Protein Sci."},{"key":"2026102207422950300_cit3","doi-asserted-by":"publisher","first-page":"37215","DOI":"10.1074\/jbc.M703800200","article-title":"Binding of\nRac1, Rnd1, and RhoD to a Novel Rho GTPase Interaction Motif Destabilizes\nDimerization of the Plexin-B1 Effector Domain","volume":"282","author":"Tong","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2026102207422950300_cit4","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.str.2007.12.012","article-title":"Insights into Oncogenic\nMutations of Plexin-B1 Based on the Solution Structure of the Rho\nGTPase Binding Domain","volume":"16","author":"Tong","year":"2008","journal-title":"Structure"},{"key":"2026102207422950300_cit5","doi-asserted-by":"publisher","first-page":"3765","DOI":"10.1007\/s00018-012-1019-0","article-title":"Plexin Structures Are\nComing: Opportunities for Multilateral Investigations\nof Semaphorin Guidance Receptors, Their Cell Signaling Mechanisms\nand Functions","volume":"69","author":"Hota","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"2026102207422950300_cit6","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1021\/acs.jpcb.8b10801","article-title":"Local Ordering\nat Mobile Sites in Proteins: Combining Perspectives from NMR Relaxation\nand Molecular Dynamics","volume":"123","author":"Tchaicheeyan","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"2026102207422950300_cit7","doi-asserted-by":"publisher","first-page":"8019","DOI":"10.1021\/acs.jpcb.9b05905","article-title":"Local Ordering\nat the N\u2013H Sites of the Rho GTPase Binding Domain of Plexin-B1:\nImpact of Dimerization","volume":"123","author":"Mendelman","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"2026102207422950300_cit8","doi-asserted-by":"publisher","first-page":"9323","DOI":"10.1021\/acs.jpcb.0c05846","article-title":"Conformational\nEntropy from Mobile Bond Vectors in Proteins: A Viewpoint that Unifies\nNMR Relaxation Theory and Molecular Dynamics Simulation Approaches","volume":"124","author":"Mendelman","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"2026102207422950300_cit9","doi-asserted-by":"publisher","first-page":"6396","DOI":"10.1021\/acs.jpcb.2c03431","article-title":"Microsecond MD Simulations of the\nPlexin-B1 RBD: N\u2013H\nProbability Density as Descriptor of Structural Dynamics, Dimerization-Related\nConformational Entropy, and Transient Dimer Asymmetry","volume":"126","author":"Pshetitsky","year":"2022","journal-title":"J. Phys. Chem. 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The Role of Symmetry\nin GTPase Binding and Dimer Formation","volume":"128","author":"Pshetitsky","year":"2024","journal-title":"J. Phys.\nChem. B"},{"key":"2026102207422950300_cit13","volume-title":"Angular Momentum:\nUnderstanding Spatial Aspects in Chemistry and Physics","author":"Zare","year":"1988"},{"key":"2026102207422950300_cit14","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.6c03042","article-title":"Peptide-Plane\nDynamics in Protein Loops from Microsecond Molecular Dynamics: A Symmetry-Based\nPerspective","author":"Pshetitsky","year":"2026","journal-title":"J. Phys. Chem. B"},{"key":"2026102207422950300_cit15","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1002\/jcc.21287","article-title":"CHARMM: the biomolecular simulation program","volume":"30","author":"Brooks","year":"2009","journal-title":"J. Comput. 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