{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:17:45Z","timestamp":1788167865334,"version":"build-2803163510"},"reference-count":85,"publisher":"American Chemical Society (ACS)","issue":"16","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001777","name":"University of Wollongong","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001777","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Australian Research Council Centre of Excellence in Quantum Biotechnology","doi-asserted-by":"publisher","award":["CE230100021"],"award-info":[{"award-number":["CE230100021"]}],"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>Amyloid beta (A\u03b2), one of the hallmark proteins of Alzheimer\u2019s disease (AD), aggregates into plaques that are strongly linked to cognitive decline and neuronal death. Reducing its aggregation propensity may provide a strategy to slow the progression of AD. While chirality modulation has emerged as an innovative approach to disrupt this process, research has primarily focused on alterations at the C\u03b1 position, often overlooking the impact of the second chiral center, such as the C\u03b2 atom of threonine. Furthermore, the underlying mechanisms governing these chiral effects remain elusive. Given the intrinsically disordered nature of the A\u03b2 peptide, we employed temperature-replica exchange molecular dynamics simulations to explore its rugged conformational landscape. We considered sequence mutations (A2T and A2V), N-terminal chirality inversion of the first six residues (A2V1\u20136D and WT1\u20136D), and alteration of the second chiral center (C\u03b2) of threonine (A2TC\u03b2). By analyzing the effect size and population change induced by these mutations and chiral modulation, we concluded that the modulation at the N-termini is not confined locally but also exerts specific effects on the central hydrophobic core (CHC) region. Inspection of their free energy landscape and representative structures reveals that the protective or pathogenic effects of these variants correlate with their similarity to the wild type ensemble. Beyond these static thermodynamics analyses, a direct connection to phase transitions was made by estimating heat capacity as a function of temperature. Both analyses predict that A2TC\u03b2 may exert a pathogenic effect, in contrast to the protective nature of A2T. These findings offer a deeper understanding of the effects of site-specific mutations and chirality and shed light on the development of advanced therapeutic strategies for AD.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01001","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:23:18Z","timestamp":1785849798000},"page":"10156-10167","source":"Crossref","is-referenced-by-count":0,"title":["N-Terminal\nChirality and Sequence Variations\nModulate the Conformational Landscape of Amyloid-Beta 42"],"prefix":"10.1021","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5612-0728","authenticated-orcid":true,"given":"Qiang","family":"Zhu","sequence":"first","affiliation":[{"name":"University of Wollongong , , , ,","place":["Wollongong, New South Wales, Australia, 2522"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-2803","authenticated-orcid":true,"given":"Haibo","family":"Yu","sequence":"additional","affiliation":[{"name":"University of Wollongong , , , ,","place":["Wollongong, New South Wales, Australia, 2522"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026083104330064600_cit1","doi-asserted-by":"publisher","first-page":"e1534","DOI":"10.1016\/S2214-109X(24)00264-X","article-title":"The global macroeconomic\nburden of Alzheimer\u2019s disease and other dementias: estimates\nand projections for 152 countries or territories","volume":"12","author":"Chen","year":"2024","journal-title":"Lancet Global Health"},{"key":"2026083104330064600_cit2","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1002\/alz.13016","article-title":"Alzheimer\u2019s\ndisease facts and figures","volume":"19","author":"Better","year":"2023","journal-title":"Alzheimers Dement"},{"key":"2026083104330064600_cit3","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.tibs.2011.02.002","article-title":"Recent progress in understanding\nAlzheimer\u2019s \u03b2-amyloid structures","volume":"36","author":"Fa\u0308ndrich","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"2026083104330064600_cit4","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid Hypothesis\nof Alzheimer\u2019s Disease:\nProgress and Problems on the Road to Therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"2026083104330064600_cit5","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.cell.2005.02.008","article-title":"Twenty Years of the\nAlzheimer\u2019s Disease Amyloid\nHypothesis: A Genetic Perspective","volume":"120","author":"Tanzi","year":"2005","journal-title":"Cell"},{"key":"2026083104330064600_cit6","doi-asserted-by":"publisher","first-page":"4693","DOI":"10.1021\/bi00069a001","article-title":"The carboxy\nterminus of the. beta.\namyloid protein is critical for the seeding of amyloid formation:\nImplications for the pathogenesis of Alzheimer\u2019s disease","volume":"32","author":"Jarrett","year":"1993","journal-title":"Biochemistry"},{"key":"2026083104330064600_cit7","doi-asserted-by":"publisher","first-page":"9758","DOI":"10.1073\/pnas.1218402110","article-title":"Proliferation\nof amyloid-\u03b242\naggregates occurs through a secondary nucleation mechanism","volume":"110","author":"Cohen","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026083104330064600_cit8","doi-asserted-by":"publisher","first-page":"9384","DOI":"10.1073\/pnas.1401564111","article-title":"Differences\nin nucleation behavior underlie the contrasting aggregation kinetics\nof the A\u03b240 and A\u03b242 peptides","volume":"111","author":"Meisl","year":"2014","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"key":"2026083104330064600_cit9","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1021\/acs.jcim.3c01624","article-title":"Structure Comparison of Beta Amyloid\nPeptide A\u03b2 1\u201342 Isoforms. Molecular Dynamics Modeling","volume":"64","author":"Tolstova","year":"2024","journal-title":"J. Chem. Inf. Model."},{"key":"2026083104330064600_cit10","doi-asserted-by":"publisher","first-page":"8401","DOI":"10.1021\/acsomega.8b00887","article-title":"Key Residues\nfor the Formation of\nA\u03b242 Amyloid Fibrils","volume":"3","author":"Hsu","year":"2018","journal-title":"ACS Omega"},{"key":"2026083104330064600_cit11","doi-asserted-by":"publisher","first-page":"12434","DOI":"10.1038\/s41598-017-10845-6","article-title":"Identification of key regions and\nresidues controlling A\u03b2 folding and assembly","volume":"7","author":"Hayden","year":"2017","journal-title":"Sci. Rep."},{"key":"2026083104330064600_cit12","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1021\/jacs.7b10343","article-title":"Pathways of\nAmyloid-\u03b2 Aggregation\nDepend on Oligomer Shape","volume":"140","author":"Barz","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"2026083104330064600_cit13","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1039\/D1SC02990H","article-title":"Amyloid-\u03b2 peptide 37, 38 and\n40 individually and cooperatively\ninhibit amyloid-\u03b2 42 aggregation","volume":"13","author":"Braun","year":"2022","journal-title":"Chem.\nSci."},{"key":"2026083104330064600_cit14","doi-asserted-by":"publisher","first-page":"19926","DOI":"10.1073\/pnas.2002570117","article-title":"Differences\nin the free energies\nbetween the excited states of A\u03b2 40 and A\u03b2 42 monomers\nencode their aggregation propensities","volume":"117","author":"Chakraborty","year":"2020","journal-title":"Proc.\nNatl. Acad. Sci. U. S. A."},{"key":"2026083104330064600_cit15","doi-asserted-by":"publisher","first-page":"5169","DOI":"10.1021\/acs.jctc.9b00599","article-title":"Modulation\nof Amyloid-\u03b242 Conformation by Small Molecules Through Nonspecific\nBinding","volume":"15","author":"Liang","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104330064600_cit16","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1111\/j.1742-4658.2010.07568.x","article-title":"Amyloid oligomers: formation and\ntoxicity of A\u03b2 oligomers","volume":"277","author":"Sakono","year":"2010","journal-title":"FEBS J."},{"key":"2026083104330064600_cit17","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.1002\/cbic.200900321","article-title":"Copper and\nZinc Binding to Amyloid-\u03b2: Coordination, Dynamics, Aggregation,\nReactivity and Metal-Ion Transfer","volume":"10","author":"Faller","year":"2009","journal-title":"ChemBioChem"},{"key":"2026083104330064600_cit18","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.jmb.2003.11.046","article-title":"Two Types\nof Alzheimer\u2019s \u03b2-Amyloid (1\u201340) Peptide Membrane\nInteractions: Aggregation Preventing Transmembrane Anchoring Versus\nAccelerated Surface Fibril Formation","volume":"335","author":"Bokvist","year":"2004","journal-title":"J. Mol.\nBiol."},{"key":"2026083104330064600_cit19","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1703","article-title":"A brief history\nof amyloid aggregation simulations","volume":"14","author":"Fatafta","year":"2024","journal-title":"Wiley Interdiscip.\nRev.:Comput. Mol. Sci."},{"key":"2026083104330064600_cit20","doi-asserted-by":"publisher","first-page":"3518","DOI":"10.1021\/cr500638n","article-title":"Amyloid \u03b2 Protein\nand Alzheimer\u2019s Disease: When Computer\nSimulations Complement Experimental Studies","volume":"115","author":"Nasica-Labouze","year":"2015","journal-title":"Chem. Rev."},{"key":"2026083104330064600_cit21","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1126\/science.1168979","article-title":"A Recessive Mutation in the APP Gene with Dominant-Negative\nEffect on Amyloidogenesis","volume":"323","author":"Di Fede","year":"2009","journal-title":"Science"},{"key":"2026083104330064600_cit22","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nature11283","article-title":"A mutation in APP protects against Alzheimer\u2019s\ndisease and\nage-related cognitive decline","volume":"488","author":"Jonsson","year":"2012","journal-title":"Nature"},{"key":"2026083104330064600_cit23","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/nn0901-887","article-title":"The \u201cArctic\u201d\nAPP mutation (E693G) causes Alzheimer\u2019s disease by enhanced\nA\u03b2 protofibril formation","volume":"4","author":"Nilsberth","year":"2001","journal-title":"Nat. Neurosci."},{"key":"2026083104330064600_cit24","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1001\/archneurol.2010.178","article-title":"Hereditary Cerebral Hemorrhage With Amyloidosis\nAssociated With the E693K Mutation of APP","volume":"67","author":"Bugiani","year":"2010","journal-title":"Arch.\nNeurology"},{"key":"2026083104330064600_cit25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cbpa.2021.01.003","article-title":"Understanding and\ncontrolling amyloid aggregation with\nchirality","volume":"64","author":"Foley","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"2026083104330064600_cit26","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1039\/D3TB02381H","article-title":"Chiral nanomaterial-based approaches\nfor diagnosis\nand treatment of protein-aggregated neurodiseases: current status\nand future opportunities","volume":"12","author":"Pranav","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"2026083104330064600_cit27","doi-asserted-by":"publisher","first-page":"12433","DOI":"10.1038\/s41598-017-10525-5","article-title":"Using chirality to probe the conformational dynamics\nand assembly of intrinsically disordered amyloid proteins","volume":"7","author":"Raskatov","year":"2017","journal-title":"Sci. Rep."},{"key":"2026083104330064600_cit28","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1038\/s41586-025-09244-z","article-title":"How short peptides disassemble\ntau fibrils in Alzheimer\u2019s\ndisease","volume":"644","author":"Hou","year":"2025","journal-title":"Nature"},{"key":"2026083104330064600_cit29","doi-asserted-by":"publisher","first-page":"20949","DOI":"10.1038\/srep20949","article-title":"Tackling amyloidogenesis in Alzheimer\u2019s\ndisease with A2V variants of Amyloid-\u03b2","volume":"6","author":"Di Fede","year":"2016","journal-title":"Sci. Rep."},{"key":"2026083104330064600_cit30","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.1021\/acschemneuro.2c00504","article-title":"Role of Hydrophobicity\nat the N-Terminal Region of A\u03b242 in Secondary Nucleation","volume":"13","author":"Thacker","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"2026083104330064600_cit31","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1021\/acs.jpcb.5b09379","article-title":"Characterization of A\u03b2 Monomers\nthrough the Convergence of Ensemble Properties among Simulations with\nMultiple Force Fields","volume":"120","author":"Rosenman","year":"2016","journal-title":"J. Phys. Chem. B"},{"key":"2026083104330064600_cit32","doi-asserted-by":"publisher","first-page":"3286","DOI":"10.1002\/prot.24669","article-title":"Dual effects of familial Alzheimer\u2019s\ndisease mutations (D7H, D7N, and H6R) on amyloid \u03b2 peptide:\nCorrelation dynamics and zinc binding","volume":"82","author":"Xu","year":"2014","journal-title":"Proteins:Struct.,\nFunct., Bioinf."},{"key":"2026083104330064600_cit33","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.1021\/ct1006967","article-title":"Distinct Morphologies for Amyloid\nBeta Protein Monomer: A\u03b21\u201340, A\u03b21\u201342, and\nA\u03b21\u201340(D23N)","volume":"7","author":"Co\u0302te\u0301","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104330064600_cit34","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.jmb.2008.09.039","article-title":"Amyloid \u03b2-Protein Monomer Folding: Free-Energy\nSurfaces Reveal Alloform-Specific Differences","volume":"384","author":"Yang","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2026083104330064600_cit35","doi-asserted-by":"publisher","first-page":"6035","DOI":"10.1021\/acs.jpcb.6c01000","article-title":"The monomeric\nconformational ensembles of A\u03b240\nand A\u03b242 encode their differential amyloid aggregation propensity","volume":"130","author":"Cadenelli","year":"2026","journal-title":"J. Phys. Chem. B"},{"key":"2026083104330064600_cit36","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1021\/acs.jpclett.2c03729","article-title":"Familial Alzheimer\u2019s\nDisease-Related Mutations Differentially Alter Stability of Amyloid-Beta\nAggregates","volume":"14","author":"Rezaei-Ghaleh","year":"2023","journal-title":"J. Phys. Chem. Lett."},{"key":"2026083104330064600_cit37","doi-asserted-by":"publisher","first-page":"3993","DOI":"10.1021\/acs.jpclett.0c00922","article-title":"Interaction Volume\nIs a Measure of the Aggregation\nPropensity of Amyloid-\u03b2","volume":"11","author":"Aggarwal","year":"2020","journal-title":"J. Phys. Chem.\nLett."},{"key":"2026083104330064600_cit38","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1021\/acs.jcim.0c01286","article-title":"Hydration Thermodynamics\nof the N-Terminal FAD Mutants\nof Amyloid-\u03b2","volume":"61","author":"Aggarwal","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"2026083104330064600_cit39","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/protein\/gzu037","article-title":"Nature versus\ndesign:\nthe conformational propensities of d-amino acids and the importance\nof side chain chirality","volume":"27","author":"Towse","year":"2014","journal-title":"Protein Eng., Des.\nSel."},{"key":"2026083104330064600_cit40","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1056\/NEJMoa2305032","article-title":"Trial of\nSolanezumab\nin Preclinical Alzheimer\u2019s Disease","volume":"389","author":"Sperling","year":"2023","journal-title":"N.\nEngl. J. Med."},{"key":"2026083104330064600_cit41","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1021\/acschemneuro.7b00037","article-title":"N-Terminal\nHypothesis for Alzheimer\u2019s\nDisease","volume":"8","author":"Murray","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"2026083104330064600_cit42","doi-asserted-by":"publisher","first-page":"7326","DOI":"10.1021\/acs.chemmater.5c01589","article-title":"Hydrogen\nBond\u2013Driven N-Terminal Amyloid \u03b2 Mimetics Attenuate Neurotoxic\nAggregation","volume":"37","author":"Kong","year":"2025","journal-title":"Chem. Mater."},{"key":"2026083104330064600_cit43","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1002\/prot.26495","article-title":"Metastable\nalpha-rich and beta-rich\nconformations of small A\u03b242 peptide oligomers","volume":"93","author":"Nguyen","year":"2025","journal-title":"Proteins:Struct., Funct., Bioinf."},{"key":"2026083104330064600_cit44","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.bpj.2017.12.025","article-title":"Highly Disordered Amyloid-\u03b2 Monomer Probed by\nSingle-Molecule FRET and MD Simulation","volume":"114","author":"Meng","year":"2018","journal-title":"Biophys.\nJ."},{"key":"2026083104330064600_cit45","doi-asserted-by":"publisher","first-page":"8160","DOI":"10.1523\/JNEUROSCI.4809-05.2006","article-title":"Prefibrillar Amyloid\nAggregates Could Be Generic Toxins in Higher Organisms","volume":"26","author":"Baglioni","year":"2006","journal-title":"J. Neurosci."},{"key":"2026083104330064600_cit46","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/416507a","article-title":"Inherent toxicity of\naggregates implies a common mechanism\nfor protein misfolding diseases","volume":"416","author":"Bucciantini","year":"2002","journal-title":"Nature"},{"key":"2026083104330064600_cit47","doi-asserted-by":"publisher","first-page":"10866","DOI":"10.1073\/pnas.1605104113","article-title":"A\u03b242 assembles into specific\n\u03b2-barrel pore-forming oligomers in membrane-mimicking environments","volume":"113","author":"Serra-Batiste","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026083104330064600_cit48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2116736119","article-title":"Single-molecule fluorescence imaging and deep learning\nreveal highly heterogeneous aggregation of amyloid-\u03b2 42","volume":"119","author":"Meng","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026083104330064600_cit49","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.jmb.2008.04.028","article-title":"Structures and Free-Energy Landscapes\nof the Wild Type and Mutants of the A\u03b221\u201330 Peptide Are\nDetermined by an Interplay between Intrapeptide Electrostatic and\nHydrophobic Interactions","volume":"379","author":"Tarus","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2026083104330064600_cit50","doi-asserted-by":"publisher","first-page":"3342","DOI":"10.1073\/pnas.96.7.3342","article-title":"Evolution\nof amyloid: What normal protein folding may tell us about fibrillogenesis\nand disease","volume":"96","author":"Lansbury","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026083104330064600_cit51","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0009-2614(99)01123-9","article-title":"Replica-exchange molecular dynamics\nmethod for protein\nfolding","volume":"314","author":"Sugita","year":"1999","journal-title":"Chem. Phys. Lett."},{"key":"2026083104330064600_cit52","doi-asserted-by":"publisher","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","article-title":"AmberTools","volume":"63","author":"Case","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"2026083104330064600_cit53","doi-asserted-by":"publisher","first-page":"104108","DOI":"10.1063\/1.5078615","article-title":"The combined\nforce field-sampling\nproblem in simulations of disordered amyloid-\u03b2 peptides","volume":"150","author":"Lincoff","year":"2019","journal-title":"J. Chem. Phys."},{"key":"2026083104330064600_cit54","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX:\nTools for structure\nbuilding and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"2026083104330064600_cit55","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1021\/acs.jctc.6b00429","article-title":"Molecular Dynamics Simulations of Intrinsically Disordered\nProteins: On the Accuracy of the TIP4P-D Water Model and the Representativeness\nof Protein Disorder Models","volume":"12","author":"Henriques","year":"2016","journal-title":"J. Chem. Theory\nComput."},{"key":"2026083104330064600_cit56","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1021\/acs.jctc.8b01123","article-title":"General\nPurpose Water Model Can Improve\nAtomistic Simulations of Intrinsically Disordered Proteins","volume":"15","author":"Shabane","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104330064600_cit57","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/prot.21123","article-title":"Comparison of multiple Amber force\nfields and development of improved protein backbone parameters","volume":"65","author":"Hornak","year":"2006","journal-title":"Proteins:Struct., Funct., Bioinf."},{"key":"2026083104330064600_cit58","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1002\/pro.3064","article-title":"Comparison of force fields for Alzheimer\u2019s A:\nA case study for intrinsically disordered proteins","volume":"26","author":"Carballo-Pacheco","year":"2017","journal-title":"Protein Sci."},{"key":"2026083104330064600_cit59","doi-asserted-by":"publisher","first-page":"23186","DOI":"10.1074\/jbc.M109.086496","article-title":"Effects\nof the English (H6R) and\nTottori (D7N) Familial Alzheimer Disease Mutations on Amyloid \u03b2-Protein\nAssembly and Toxicity","volume":"285","author":"Ono","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2026083104330064600_cit60","doi-asserted-by":"publisher","first-page":"024111","DOI":"10.1063\/1.1831273","article-title":"Optimal allocation\nof replicas in\nparallel tempering simulations","volume":"122","author":"Rathore","year":"2004","journal-title":"J. Chem. Phys."},{"key":"2026083104330064600_cit61","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian\nequations of motion of a system with constraints: molecular dynamics\nof n-alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"2026083104330064600_cit62","unstructured":"Case, D.; et al.; Amber 2024; University of\nCalifornia: San Francisco, 2024."},{"key":"2026083104330064600_cit63","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1016\/j.bpj.2015.08.015","article-title":"MDTraj:\nA Modern Open Library for the Analysis of Molecular\nDynamics Trajectories","volume":"109","author":"McGibbon","year":"2015","journal-title":"Biophys. J."},{"key":"2026083104330064600_cit64","first-page":"2825","article-title":"Scikit-learn: Machine\nLearning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J.\nMach. Learn. Res."},{"key":"2026083104330064600_cit65","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1021\/ja036813f","article-title":"Solution\nNMR Studies of the A\u03b2(1\u201340) and\nA\u03b2(1\u201342) Peptides Establish that the Met35 Oxidation\nState Affects the Mechanism of Amyloid Formation","volume":"126","author":"Hou","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"2026083104330064600_cit66","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1002\/cbic.201402595","article-title":"Solution NMR\nStudies of Recombinant A\u03b2(1\u201342): From the Presence of\na Micellar Entity to Residual \u03b2-Sheet Structure in the Soluble\nSpecies","volume":"16","author":"Wa\u0308lti","year":"2015","journal-title":"ChemBioChem"},{"key":"2026083104330064600_cit67","doi-asserted-by":"publisher","first-page":"4266","DOI":"10.1021\/acs.jctc.5c00026","article-title":"LEGOLAS: A Machine Learning Method\nfor Rapid and Accurate Predictions of Protein NMR Chemical Shifts","volume":"21","author":"Darrows","year":"2025","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104330064600_cit68","doi-asserted-by":"publisher","first-page":"4655","DOI":"10.1021\/acs.jpcb.4c00503","article-title":"Exploring\nStructural Insights of A\u03b242 and \u03b1-Synuclein Monomers and\nHeterodimer: A Comparative Study Using Implicit and Explicit Solvent\nSimulations","volume":"128","author":"Varenyk","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"2026083104330064600_cit69","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving\nthe Accuracy of\nProtein Side Chain and Backbone Parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104330064600_cit70","doi-asserted-by":"publisher","first-page":"234505","DOI":"10.1063\/1.2121687","article-title":"A general purpose model for the condensed phases of\nwater: TIP4P\/2005","volume":"123","author":"Abascal","year":"2005","journal-title":"J. Chem. Phys."},{"key":"2026083104330064600_cit71","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1074\/jbc.270.7.3063","article-title":"The \u03b1-Helical\nto \u03b2-Strand Transition in the Amino-terminal Fragment of the\nAmyloid \u03b2-Peptide Modulates Amyloid Formation","volume":"270","author":"Soto","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2026083104330064600_cit72","doi-asserted-by":"publisher","first-page":"8545","DOI":"10.1074\/jbc.271.15.8545","article-title":"Arrest of\nbeta-Amyloid Fibril Formation by a Pentapeptide Ligand","volume":"271","author":"Tjernberg","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2026083104330064600_cit73","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1093\/bioinformatics\/btn432","article-title":"Optimal contact map alignment of\nprotein\u2013protein interfaces","volume":"24","author":"Pulim","year":"2008","journal-title":"Bioinformatics"},{"key":"2026083104330064600_cit74","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1021\/acschemneuro.7b00412","article-title":"Weaker N-Terminal Interactions for\nthe Protective over the Causative A\u03b2 Peptide Dimer Mutants","volume":"9","author":"Sharma","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"2026083104330064600_cit75","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600749113","article-title":"Atomic-resolution\nstructure of a disease-relevant A\u03b2(1\u201342) amyloid fibril","volume":"113","author":"Wa\u0308lti","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026083104330064600_cit76","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/prot.20310","article-title":"Energy landscape of a small peptide\nrevealed by dihedral angle principal component analysis","volume":"58","author":"Mu","year":"2005","journal-title":"Proteins:Struct., Funct., Bioinf."},{"key":"2026083104330064600_cit77","first-page":"226","volume-title":"A Density-Based Algorithm for Discovering\nClusters in Large Spatial Databases with Noise","author":"Ester","year":"1996"},{"key":"2026083104330064600_cit78","doi-asserted-by":"publisher","first-page":"12289","DOI":"10.1021\/acs.jctc.5c01133","article-title":"Characterizing Structural and Kinetic\nEnsembles of Intrinsically Disordered Proteins Using Writhe","volume":"21","author":"Sisk","year":"2025","journal-title":"J. Chem. Theory Comput."},{"key":"2026083104330064600_cit79","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10711-008-9247-z","article-title":"Parabolic section and distance excess of space curves\napplied to protein structure classification","volume":"134","author":"R\u00f8gen","year":"2008","journal-title":"Geom. Dedicata"},{"key":"2026083104330064600_cit80","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add6921","article-title":"Energy landscapes\nof A\u03b2 monomers\nare sculpted in accordance with Ostwald\u2019s rule of stages","volume":"9","author":"Chakraborty","year":"2023","journal-title":"Sci. Adv."},{"key":"2026083104330064600_cit81","doi-asserted-by":"publisher","first-page":"17749","DOI":"10.1038\/s41598-017-18012-7","article-title":"Entropy and Polarity\nControl the Partition and Transportation of Drug-like Molecules in\nBiological Membrane","volume":"7","author":"Zhu","year":"2017","journal-title":"Sci. Rep."},{"key":"2026083104330064600_cit82","doi-asserted-by":"publisher","first-page":"195101","DOI":"10.1063\/5.0299580","article-title":"Modeling the dimerization of amyloid-\u03b2(1\u201340)\nand amyloid-\u03b2(1\u201342)","volume":"163","author":"Sommerfeld","year":"2025","journal-title":"J. Chem. Phys."},{"key":"2026083104330064600_cit83","doi-asserted-by":"publisher","first-page":"180601","DOI":"10.1103\/PhysRevLett.120.180601","article-title":"Classification of Phase Transitions by Microcanonical\nInflection-Point Analysis","volume":"120","author":"Qi","year":"2018","journal-title":"Phys. Rev. Lett."},{"key":"2026083104330064600_cit84","doi-asserted-by":"publisher","first-page":"011127","DOI":"10.1103\/PhysRevE.84.011127","article-title":"Microcanonical entropy\ninflection points: Key to systematic understanding of transitions\nin finite systems","volume":"84","author":"Schnabel","year":"2011","journal-title":"Phys. Rev. E:Stat., Nonlinear,\nSoft Matter Phys."},{"key":"2026083104330064600_cit85","doi-asserted-by":"crossref","DOI":"10.1142\/4340","volume-title":"Microcanonical Thermodynamics:\nPhase Transitions In\u201d Small\u201d Systems","author":"Gross","year":"2001"}],"container-title":["Journal of Chemical Information\nand Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.6c01001","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/16\/10156\/66343180\/acs.jcim.6c01001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/16\/10156\/66343180\/acs.jcim.6c01001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:33:47Z","timestamp":1788165227000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/66\/16\/10156\/5237418\/N-Terminal-Chirality-and-Sequence-Variations"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":85,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,7,30]]},"published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.6c01001","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}