{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:17:29Z","timestamp":1788167849521,"version":"build-2803163510"},"reference-count":53,"publisher":"American Chemical Society (ACS)","issue":"16","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2025YFHZ0065"],"award-info":[{"award-number":["2025YFHZ0065"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103483"],"award-info":[{"award-number":["82103483"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574020"],"award-info":[{"award-number":["82574020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2503700"],"award-info":[{"award-number":["2022YFC2503700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2503703"],"award-info":[{"award-number":["2022YFC2503703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Internal Collaboration Project of Jiangsu Radiological Medicine Collaborative Innovation Center","doi-asserted-by":"publisher","award":["FY202401"],"award-info":[{"award-number":["FY202401"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Key Laboratory of Radiation Damage and Countermeasures of Jiangsu Provincial Universities and Colleges","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Suzhou Fundamental Research Project","doi-asserted-by":"publisher","award":["SJC2023001"],"award-info":[{"award-number":["SJC2023001"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rac1 is a small GTPase of the Rho family. It is a central regulator of cytoskeletal remodeling, cell adhesion, migration, and secretion. Dysregulation of Rac1 activity drives tumorigenesis, with the cancer-associated P29S mutation ranking as the third most frequently mutated proto-oncogene in sun-exposed melanoma. P29S is a prototypical gain-of-function, fast-cycling variant that destabilizes GDP binding and accelerates nucleotide exchange. Another cancer-associated mutant, F28L, produces cellular phenotypes strikingly similar to those of P29S yet has been proposed to act through a distinct local structural perturbation, raising the question of whether they share a common activation mechanism. Defining this shared mechanism is critical for understanding Rac1-driven oncogenesis and for guiding the rational design of inhibitors that effectively target these activating mutations. Here, integrating molecular dynamics simulations, potential of mean force calculations, and biochemical assays, we show that P29S, F28L, and the structurally distinct L160C mutant all weaken GDP binding while enhancing GTP affinity\u2500revealing an oncogenic mechanism beyond fast cycling. Structural dynamic analyses uncover a shared \u201cteeter-totter-like\u201d redistribution of the Switch I region, in which destabilization of its N-terminal hydrophobic core is coupled to reinforcement of its C-terminal contact network. This dynamic shift strengthens effector binding, as validated by GTPase pull-down assays, and is also reproduced by other cancer-associated mutants in Rac1 (I21S, P34S, D57E). Our findings identify the \u03b26\u2212\u03b15 loop as an allosteric hub linking nucleotide binding to effector engagement and suggest that rebalancing the Switch I region may provide a therapeutic strategy to counteract Rac1-driven oncogenic signaling.<\/jats:p>","DOI":"10.1021\/acs.jcim.5c02116","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:02:19Z","timestamp":1785934939000},"page":"10033-10045","source":"Crossref","is-referenced-by-count":0,"title":["Teeter-Totter-Like\nRedistribution of Switch I: Integrating\nSimulation and Experiment to Uncover the Molecular Basis of Oncogenic\nRac1Mutations"],"prefix":"10.1021","volume":"66","author":[{"given":"Shuo","family":"Li","sequence":"first","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Hu","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Navy Military Medical University , , 225 Changhai Road , ,","place":["Shanghai, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-9377","authenticated-orcid":true,"given":"Shengtang","family":"Liu","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Navy Military Medical University , , 225 Changhai Road , ,","place":["Shanghai, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3521-6867","authenticated-orcid":true,"given":"Zaixing","family":"Yang","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310027"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jiao","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-6552","authenticated-orcid":true,"given":"Xuanyu","family":"Meng","sequence":"additional","affiliation":[{"name":"Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"2026083104324770900_cit1","doi-asserted-by":"publisher","first-page":"5445","DOI":"10.1158\/0008-5472.CAN-17-1456","article-title":"The Rac GTPase in Cancer: From Old Concepts to New\nParadigms","volume":"77","author":"Kazanietz","year":"2017","journal-title":"Cancer Res."},{"key":"2026083104324770900_cit2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1152\/physrev.2001.81.1.153","article-title":"Small GTP-binding proteins","volume":"81","author":"Takai","year":"2001","journal-title":"Physiol. Rev."},{"key":"2026083104324770900_cit3","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.2741\/3872","article-title":"Role of\nRho GTPases and their regulators\nin cancer progression","volume":"16","author":"Rathinam","year":"2011","journal-title":"Front. Biosci.-Landmark"},{"key":"2026083104324770900_cit4","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s10585-007-9119-1","article-title":"Rho GTPases: functions and association with cancer","volume":"24","author":"Ellenbroek","year":"2007","journal-title":"Clin. Exp. Metastasis"},{"key":"2026083104324770900_cit5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nrm.2015.14","article-title":"The front\nand rear of collective cell migration","volume":"17","author":"Mayor","year":"2016","journal-title":"Nat.\nRev. Mol. Cell Biol."},{"key":"2026083104324770900_cit6","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1146\/annurev.biochem.72.121801.161742","article-title":"Biology\nof the p21-activated kinases","volume":"72","author":"Bokoch","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"2026083104324770900_cit7","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3390\/cancers12030665","article-title":"Rac1 Signaling: From\nIntestinal Homeostasis to Colorectal\nCancer Metastasis","volume":"12","author":"Kotelevets","year":"2020","journal-title":"Cancers"},{"key":"2026083104324770900_cit8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1247\/csf.15003","article-title":"IQGAPs as Key Regulators of Actin-cytoskeleton\nDynamics","volume":"40","author":"Watanabe","year":"2015","journal-title":"Cell Struct. Funct."},{"key":"2026083104324770900_cit9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1080\/21541248.2017.1321169","article-title":"New model for the interaction of\nIQGAP1 with CDC42 and RAC1","volume":"11","author":"Nouri","year":"2020","journal-title":"Small GTPases"},{"key":"2026083104324770900_cit10","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1038\/sj.embor.7400293","article-title":"Always look on the\nbright site of Rho: structural implications\nfor a conserved intermolecular interface","volume":"5","author":"Dvorsky","year":"2004","journal-title":"EMBO\nRep."},{"key":"2026083104324770900_cit11","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.cell.2012.06.024","article-title":"A Landscape of Driver Mutations in\nMelanoma","volume":"150","author":"Hodis","year":"2012","journal-title":"Cell"},{"key":"2026083104324770900_cit12","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1073\/pnas.1216141110","article-title":"Transforming\nmutations of RAC guanosine triphosphatases in human cancers","volume":"110","author":"Kawazu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026083104324770900_cit13","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1073\/pnas.1220895110","article-title":"RAC1 P29S is a spontaneously activating cancer-associated\nGTPase","volume":"110","author":"Davis","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026083104324770900_cit14","doi-asserted-by":"publisher","first-page":"3790","DOI":"10.1021\/acs.jpcb.1c00883","article-title":"Mechanistic\nDifferences of Activation of Rac1P29S and Rac1A159V","volume":"125","author":"Senyuz","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"2026083104324770900_cit15","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav8945","article-title":"Conformational landscape\nalternations promote oncogenic activities of Ras-related C3 botulinum\ntoxin substrate 1 as revealed by NMR","volume":"5","author":"Toyama","year":"2019","journal-title":"Sci. Adv."},{"key":"2026083104324770900_cit16","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4939","article-title":"Assessing the mechanism of fast-cycling\ncancer-associated\nmutations of Rac1 small Rho GTPase","volume":"33","author":"Parise","year":"2024","journal-title":"Protein\nSci."},{"key":"2026083104324770900_cit17","doi-asserted-by":"publisher","first-page":"23633","DOI":"10.1074\/jbc.274.33.23633","article-title":"Specific contributions of the small\nGTPases Rho, Rac, and Cdc42 to Dbl transformation","volume":"274","author":"Lin","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2026083104324770900_cit18","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1091\/mbc.e10-10-0849","article-title":"Glioblastoma motility\noccurs in the absence of actin polymer","volume":"22","author":"Panopoulos","year":"2011","journal-title":"Mol.\nBiol. Cell"},{"key":"2026083104324770900_cit19","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/341209a0","article-title":"Structure\nof the guanine-nucleotide-binding domain\nof the Ha-ras oncogene product p21 in the triphosphate conformation","volume":"341","author":"Pai","year":"1989","journal-title":"Nature"},{"key":"2026083104324770900_cit20","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic\nAcids Res."},{"key":"2026083104324770900_cit21","doi-asserted-by":"publisher","first-page":"14409","DOI":"10.1038\/s41598-017-13619-2","article-title":"Allosteric\ninhibition\nof the guanine nucleotide exchange factor DOCK5 by a small molecule","volume":"7","author":"Ferrandez","year":"2017","journal-title":"Sci. Rep."},{"key":"2026083104324770900_cit22","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.bpj.2009.04.013","article-title":"CHARMM-GUI Membrane\nBuilder for mixed bilayers and its application to yeast membranes","volume":"97","author":"Jo","year":"2009","journal-title":"Biophys. J."},{"key":"2026083104324770900_cit23","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1038\/ng.2359","article-title":"Exome\nsequencing identifies recurrent somatic RAC1\nmutations in melanoma","volume":"44","author":"Krauthammer","year":"2012","journal-title":"Nat. Genet."},{"key":"2026083104324770900_cit24","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure\nprediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2026083104324770900_cit25","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/75158","article-title":"Structure of Cdc42 bound to the GTPase\nbinding domain of PAK","volume":"7","author":"Morreale","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"2026083104324770900_cit26","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S0092-8674(00)00043-X","article-title":"Structure of PAK1 in an autoinhibited conformation\nreveals a multistage activation switch","volume":"102","author":"Lei","year":"2000","journal-title":"Cell"},{"key":"2026083104324770900_cit27","volume-title":"Crystal Structure of\nHuman RAC3 in Complex\nwith CRIB Domain of Human p21-activated Kinase 1 (PAK1)","author":"Ugochukwu","year":"2007"},{"key":"2026083104324770900_cit28","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"GROMACS 4: Algorithms\nfor highly efficient, load-balanced, and scalable molecular simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104324770900_cit29","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: fast, flexible, and free","volume":"26","author":"Van Der Spoel","year":"2005","journal-title":"J. Comput. Chem."},{"key":"2026083104324770900_cit30","doi-asserted-by":"publisher","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update\nof the CHARMM all-atom additive\nforce field for lipids: validation on six lipid types","volume":"114","author":"Klauda","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"2026083104324770900_cit31","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison\nof Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"2026083104324770900_cit32","doi-asserted-by":"publisher","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical\nsampling through velocity\nrescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"2026083104324770900_cit33","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh\nEwald - an N.Log(N)\nMethod for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem.\nPhys."},{"issue":"1","key":"2026083104324770900_cit34","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual\nmolecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph"},{"key":"2026083104324770900_cit35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/pro.3235","article-title":"UCSF ChimeraX:\nMeeting\nmodern challenges in visualization and analysis","volume":"27","author":"Goddard","year":"2018","journal-title":"Protein Sci."},{"key":"2026083104324770900_cit36","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13321-021-00548-6","article-title":"ProLIF: a library\nto encode molecular interactions as fingerprints","volume":"13","author":"Bouysset","year":"2021"},{"key":"2026083104324770900_cit37","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0010-4655(95)00053-I","article-title":"The Calculation\nof the Potential of Mean Force Using Computer-Simulations","volume":"91","author":"Roux","year":"1995","journal-title":"Comput. Phys. Commun."},{"key":"2026083104324770900_cit38","doi-asserted-by":"publisher","first-page":"3713","DOI":"10.1021\/ct100494z","article-title":"g_wham-A Free Weighted Histogram\nAnalysis Implementation Including Robust Error and Autocorrelation\nEstimates","volume":"6","author":"Hub","year":"2010","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104324770900_cit39","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating Structures and Free Energies\nof Complex Molecules: Combining Molecular Mechanics and Continuum\nModels","volume":"33","author":"Kollman","year":"2000","journal-title":"Acc. Chem. Res."},{"key":"2026083104324770900_cit40","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: An Efficient\nProgram for End-State Free Energy Calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104324770900_cit41","doi-asserted-by":"publisher","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA:\nA New Tool to Perform End-State Free Energy Calculations with GROMACS","volume":"17","author":"Valde\u0301s-Tresanco","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104324770900_cit42","doi-asserted-by":"publisher","first-page":"5722","DOI":"10.1021\/jacs.6b02682","article-title":"Interaction Entropy: A New Paradigm for Highly Efficient\nand Reliable Computation of Protein\u2013Ligand Binding Free Energy","volume":"138","author":"Duan","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"2026083104324770900_cit43","doi-asserted-by":"publisher","first-page":"25341","DOI":"10.1074\/jbc.M111.236455","article-title":"Multiple factors confer\nspecific Cdc42 and Rac protein activation by dedicator of cytokinesis\n(DOCK) nucleotide exchange factors","volume":"286","author":"Kulkarni","year":"2011","journal-title":"J. Biol.\nChem."},{"key":"2026083104324770900_cit44","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3390\/sci4030032","article-title":"Benzene, an Unexpected\nBinding Unit in Anion\u2212\u03c0\nRecognition: The Critical Role of CH\/\u03c0 Interactions","volume":"4","author":"Quin\u0303onero","year":"2022","journal-title":"Sci"},{"key":"2026083104324770900_cit45","article-title":"The Catalogue of Somatic\nMutations in Cancer (COSMIC)","volume":"10","author":"Forbes","year":"2008","journal-title":"Curr. Protoc\nHum Genet"},{"key":"2026083104324770900_cit46","doi-asserted-by":"publisher","first-page":"115037","DOI":"10.1016\/j.colsurfb.2025.115037","article-title":"Molecular mechanism of self-activation\ninduced by the intrinsically disordered region in Rac1b: Structural\nand functional insights","volume":"256","author":"Li","year":"2025","journal-title":"Colloids Surf., B"},{"key":"2026083104324770900_cit47","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/S0021-9258(18)54022-9","article-title":"Kinetic and\nstructural analysis of\nthe Mg(2+)-binding site of the guanine nucleotide-binding protein\np21H-ras","volume":"268","author":"John","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2026083104324770900_cit48","doi-asserted-by":"publisher","first-page":"6379","DOI":"10.1016\/j.cell.2024.08.017","article-title":"Targeting Ras-, Rho-, and Rab-family GTPases via a\nconserved cryptic pocket","volume":"187","author":"Morstein","year":"2024","journal-title":"Cell"},{"key":"2026083104324770900_cit49","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3390\/cells7120263","article-title":"Post-Translational\nModification and Subcellular Distribution of Rac1:\nAn Update","volume":"7","author":"Abdrabou","year":"2018","journal-title":"Cells"},{"key":"2026083104324770900_cit50","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1080\/21541248.2016.1211398","article-title":"Rac1 in human diseases:\nThe therapeutic potential of\ntargeting Rac1 signaling regulatory mechanisms","volume":"8","author":"Marei","year":"2017","journal-title":"Small GTPases"},{"key":"2026083104324770900_cit51","doi-asserted-by":"publisher","first-page":"6625","DOI":"10.1073\/pnas.1419895112","article-title":"Oncogenic and RASopathy-associated\nK-RAS mutations relieve membrane-dependent\nocclusion of the effector-binding site","volume":"112","author":"Mazhab-Jafari","year":"2015","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"key":"2026083104324770900_cit52","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.bpj.2016.01.019","article-title":"Oncogenic\nK-Ras Binds to an Anionic Membrane in Two Distinct Orientations: A\nMolecular Dynamics Analysis","volume":"110","author":"Prakash","year":"2016","journal-title":"Biophys. J."},{"key":"2026083104324770900_cit53","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.bpj.2019.12.039","article-title":"The Plasma\nMembrane as a Competitive Inhibitor and\nPositive Allosteric Modulator of KRas4B Signaling","volume":"118","author":"Neale","year":"2020","journal-title":"Biophys. J."}],"container-title":["Journal of Chemical Information\nand Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.5c02116","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/16\/10033\/66378525\/acs.jcim.5c02116.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/16\/10033\/66378525\/acs.jcim.5c02116.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:33:10Z","timestamp":1788165190000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/66\/16\/10033\/5242146\/Teeter-Totter-Like-Redistribution-of-Switch-I"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":53,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8,3]]},"published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.5c02116","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}