{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:45:13Z","timestamp":1792709113304,"version":"4.5.0"},"reference-count":36,"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\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY029169"],"award-info":[{"award-number":["R01EY029169"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM112491"],"award-info":[{"award-number":["R01GM112491"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"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>We present a new description of large-scale peptide-plane dynamics occurring primarily in protein loops, based on established symmetry principles. As model system we analyze molecular dynamics (MD) simulations of the Rho GTPase-binding domain of plexin-B1 (RBD). From the MD trajectories, we derive statistical local peptide-plane-related potentials, u(\u03b8, \u03c6), and corresponding probability distributions, P(\u03b8, \u03c6) = exp[\u2212u(\u03b8, \u03c6)]. The polar angles, (\u03b8, \u03c6), describe the orientation of the probe in the protein. The time series of the peptide-plane-flanking dihedrals, (\u03a8, \u03a6), are also derived. Earlier 50\u2013100 ns RBD simulations yielded positive-\u03c6 free-energy surfaces, u(positive)(\u03b8, \u03c6), spanning the 0 \u2264 (\u03b8, \u03c6) \u2264 180\u00b0 range. To extract maximal information from these statistical functions, we explicitly approximated them by combinations of real Wigner functions, DL,K, which, like the peptide plane, exhibit D2h symmetry. Nonpolar Ag and uniquely polar-vector B2u terms were found to make the dominant contributions. Here we use 1 \u03bcs RBD simulations. Along with the previously observed u(positive)(\u03b8, \u03c6) component, a negative-\u03c6 component, u(negative)(\u03b8, \u03c6), spanning the \u03b8\u2032 = 180\u00b0 \u2013 \u03b8 and \u03c6\u2032 = \u2013 \u03c6 range, also appears. Within the overall potential, u(combined)(\u03b8, \u03c6), the two components relate by inversion and rarely interconvert, pointing phenomenologically to slow motion on the 1 \u03bcs time scale. This behavior is also evident in the time series of the peptide-plane-flanking dihedrals. The overall potential, u(combined)(\u03b8, \u03c6), is analyzed empirically. We show that Ag and B2u D2h symmetry elements are inherent to its structure. Based on the results obtained here and in the accompanying article in this issue, we establish a new symmetry-based framework for analyzing local peptide-plane dynamics, grounded in the effective D2h symmetry of the peptide plane. Actual motions are exemplified by the canonical type II \u2192 type I \u03b2-turn crankshaft flips executed by the peptide plane K50\u2013G51 of the L2 loop of the RBD. Broader applications involving diverse peptide-plane restructuring mechanisms are presented in the accompanying article.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c03042","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:02:24Z","timestamp":1791907344000},"page":"11045-11055","source":"Crossref","is-referenced-by-count":1,"title":["Peptide-Plane Dynamics\nin Protein Loops from Microsecond\nMolecular Dynamics: A Symmetry-Based Perspective"],"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":"2026102207420075300_cit1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s42004-024-01115-4","article-title":"Probing the dynamic landscape of peptides in molecular\nassemblies by synergized NMR experiments and MD simulations","volume":"7","author":"Nencini","year":"2024","journal-title":"Commun. Chem."},{"key":"2026102207420075300_cit2","doi-asserted-by":"publisher","DOI":"10.3389\/frbis.2023.1219843","article-title":"Protein structure\nand dynamics in the era of integrative structural biology","volume":"1","author":"Grandori","year":"2023","journal-title":"Front. Biophys."},{"key":"2026102207420075300_cit3","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4768","article-title":"An integrated\napproach of NMR experiments and MD simulations visualizes structural\ndynamics of a cyclic multi-domain protein","volume":"32","author":"Sorada","year":"2023","journal-title":"Protein\nSci."},{"key":"2026102207420075300_cit4","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/978-1-61779-334-9_13","article-title":"Combining NMR\nand molecular\ndynamics studies for insights into the allostery of small GTPase\u2013protein\ninteractions.","volume-title":"Allostery: Methods and Protocols","author":"Zhang","year":"2012"},{"key":"2026102207420075300_cit5","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 Rho GTPase binding\ndomain with Rnd1 and active Rac1","volume":"18","author":"Hota","year":"2009","journal-title":"Protein Sci."},{"key":"2026102207420075300_cit6","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":"2026102207420075300_cit7","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":"2026102207420075300_cit8","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":"2026102207420075300_cit9","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":"2026102207420075300_cit10","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":"2026102207420075300_cit11","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":"2026102207420075300_cit12","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. B"},{"key":"2026102207420075300_cit13","doi-asserted-by":"publisher","first-page":"6408","DOI":"10.1021\/acs.jpcb.2c03435","article-title":"Microsecond MD simulations of the\nPlexin-B1 RBD: 2.\nN-H probability densities and conformational entropy in ligand-free,\nRac1-bound, and dimer RBD","volume":"126","author":"Mendelman","year":"2022","journal-title":"J. Phys. Chem. B"},{"key":"2026102207420075300_cit14","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1021\/acs.jpcb.3c06741","article-title":"Local structures\nin proteins from microsecond molecular dynamics simulations: A symmetry-based\nperspective","volume":"128","author":"Pshetitsky","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"2026102207420075300_cit15","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1021\/acs.jpcb.3c06745","article-title":"Local structures\nin proteins from\nmicrosecond molecular dynamics simulations: 2. The role of symmetry\nin GTPase binding and dimer formation","volume":"128","author":"Pshetitsky","year":"2024","journal-title":"J. Phys.\nChem. B"},{"key":"2026102207420075300_cit16","volume-title":"Angular Momentum:\nUnderstanding Spatial Aspects in Chemistry and Physics","author":"Zare","year":"1988"},{"key":"2026102207420075300_cit17","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198520245.001.0001","volume-title":"The Physics of Liquid\nCrystals","author":"de Gennes","year":"1993"},{"key":"2026102207420075300_cit18","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/BF00211787","article-title":"Crankshaft motions\nof the polypeptide backbone in molecular dynamics simulations of human\ntype-alpha transforming growth factor","volume":"6","author":"Fadel","year":"1995","journal-title":"J. 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