{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:16:34Z","timestamp":1788466594128,"version":"build-2803163510"},"reference-count":90,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tryptophan (TRP) self-assembly is responsible for the development of several neurodegenerative disorders, such as hypertryptophanemia, for which effective therapeutics are still lacking. Although several experimental studies have demonstrated varying inhibitory efficacies of different functional moiety-rich compounds, the mechanistic role of individual functional groups while inhibiting the spontaneous self-assembly is still elusive. We have performed molecular dynamics simulations to explore different kinds of interspecies interactions between TRP and distinct functional groups present in experimentally studied aromatic and nonaromatic compounds with varying concentrations: tannic acid (TA), which contains both aromatic and hydroxyl moieties, and polyols, namely, sorbitol and mannitol, which contain no aromatic ring but only hydroxyl moieties. TA reduces TRP self-assembly more effectively than polyols, a difference not attributable solely to molecular size or multivalency. Quantitative analyses of different TRP\u2013TA interactions, including \u03c0\u2013\u03c0 stacking between aromatic rings and H-bonding between respective hydroxyl moieties, reveal that lifetimes of \u03c0\u2013\u03c0 stacking are much higher than the H-bond lifetimes. Notably, the number and strength of \u03c0\u2013\u03c0 stacking interactions dominate over the H-bonding interaction in TA-mediated inhibition, although a large number of hydroxyl groups are present in TA. Consequently, TRP exhibits longer residence times in the vicinity of TA than polyols. Furthermore, TA weakens \u03c0\u2013\u03c0 stacking between TRP molecules, reducing TRP aggregation. The computed TRP\u2013TA binding energy may therefore serve as a guide for evaluating the efficacies of other chemical compounds, demonstrating the importance of the aromatic ring in inhibiting the early stages of TRP oligomerization.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c03238","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T17:53:46Z","timestamp":1788112426000},"page":"8794-8804","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Role\nof Different Functional Groups in\nInhibiting Tryptophan Self-Assembly: Comparison between Aromatic and\nNonaromatic Hydroxyl Moiety-Rich Chemical Compounds"],"prefix":"10.1021","volume":"130","author":[{"given":"Abdul Aziz","family":"Mandal","sequence":"first","affiliation":[{"name":"S. N. Bose National Centre for Basic Sciences , , Block-JD, Sector-III, Salt Lake , ,","place":["Kolkata, India, 700106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudipta","family":"Mitra","sequence":"additional","affiliation":[{"name":"S. N. Bose National Centre for Basic Sciences , , Block-JD, Sector-III, Salt Lake , ,","place":["Kolkata, India, 700106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-0015","authenticated-orcid":true,"given":"Suman","family":"Chakrabarty","sequence":"additional","affiliation":[{"name":"S. N. Bose National Centre for Basic Sciences , , Block-JD, Sector-III, Salt Lake , ,","place":["Kolkata, India, 700106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4472-5743","authenticated-orcid":true,"given":"Ranjit","family":"Biswas","sequence":"additional","affiliation":[{"name":"S. N. Bose National Centre for Basic Sciences , , Block-JD, Sector-III, Salt Lake , ,","place":["Kolkata, India, 700106"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"1","key":"2026090315291757000_cit1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s10822-024-00557-1","article-title":"Molecular\nDynamics Simulations as a Guide for Modulating Small Molecule Aggregation","volume":"38","author":"Nesabi","year":"2024","journal-title":"J. Comput.-Aided Mol. Des"},{"key":"2026090315291757000_cit2","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.3762\/bjnano.12.85","article-title":"Self-Assembly of Amino Acids toward Functional Biomaterials","volume":"12","author":"Ren","year":"2021","journal-title":"Beilstein J. Nanotechnol"},{"key":"2026090315291757000_cit3","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/nature02264","article-title":"Folding\nProteins in Fatal Ways","volume":"426","author":"Selkoe","year":"2003","journal-title":"Nature"},{"issue":"34","key":"2026090315291757000_cit4","doi-asserted-by":"publisher","first-page":"9019","DOI":"10.1021\/acs.jpcb.6b03892","article-title":"Action of Caffeine\nas an Amyloid Inhibitor in the Aggregation of\nA\u03b2 16\u201322 Peptides","volume":"120","author":"Sharma","year":"2016","journal-title":"J.\nPhys. Chem. B"},{"key":"2026090315291757000_cit5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.sbi.2009.12.017","article-title":"Principles\nGoverning Oligomer Formation in Amyloidogenic\nPeptides","volume":"20","author":"Straub","year":"2010","journal-title":"Curr. Opin. Struct. Biol"},{"key":"2026090315291757000_cit6","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1021\/acs.chemrev.0c01122","article-title":"Amyloid Oligomers: A Joint Experimental\/Computational\nPerspective on Alzheimer\u2019s Disease, Parkinson\u2019s Disease,\nType II Diabetes, and Amyotrophic Lateral Sclerosis","volume":"121","author":"Nguyen","year":"2021","journal-title":"Chem. Rev"},{"issue":"48","key":"2026090315291757000_cit7","doi-asserted-by":"publisher","first-page":"30525","DOI":"10.1039\/C8CP06239K","article-title":"Self-Assembly of Aromatic Amino Acids:\nA Molecular Dynamics Study","volume":"20","author":"Uyaver","year":"2018","journal-title":"Phys. Chem. Chem.\nPhys"},{"key":"2026090315291757000_cit8","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ymgme.2013.09.001","article-title":"Fluctuations\nin Phenylalanine Concentrations in Phenylketonuria: A Review of Possible\nRelationships with Outcomes","volume":"110","author":"Cleary","year":"2013","journal-title":"Mol. Genet. Metab"},{"issue":"8","key":"2026090315291757000_cit9","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nchembio.1002","article-title":"Phenylalanine Assembly\ninto Toxic Fibrils Suggests Amyloid Etiology in Phenylketonuria","volume":"8","author":"Adler-Abramovich","year":"2012","journal-title":"Nat. Chem. Biol"},{"key":"2026090315291757000_cit10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/0009-8981(83)90094-3","article-title":"Familial\nhypertryptophanemia, tryptophanuria\nand indoleketonuria","volume":"131","author":"Snedden","year":"1983","journal-title":"Clin. Chim. Acta"},{"issue":"4","key":"2026090315291757000_cit11","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.ymgme.2017.02.009","article-title":"Hypertryptophanemia\nDue to Tryptophan 2,3-Dioxygenase Deficiency","volume":"120","author":"Ferreira","year":"2017","journal-title":"Mol. Genet. Metab"},{"issue":"3","key":"2026090315291757000_cit12","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1021\/acschemneuro.8b00310","article-title":"Amyloid-like Structures\nFormed by Single Amino Acid Self-Assemblies of Cysteine and Methionine","volume":"10","author":"Gour","year":"2019","journal-title":"ACS Chem. Neurosci"},{"issue":"27","key":"2026090315291757000_cit13","doi-asserted-by":"publisher","first-page":"8252","DOI":"10.1021\/acs.langmuir.2c00648","article-title":"Amyloids Formed by\nNonaromatic Amino\nAcid Methionine and Its Cross with Phenylalanine Significantly Affects\nPhospholipid Vesicle Membrane: An Insight into Hypermethioninemia\nDisorder","volume":"38","author":"Nandi","year":"2022","journal-title":"Langmuir"},{"issue":"42","key":"2026090315291757000_cit14","doi-asserted-by":"publisher","first-page":"10141","DOI":"10.1039\/c3sm51054a","article-title":"Single Amino\nAcid Based Self-Assembled Structure","volume":"9","author":"Perween","year":"2013","journal-title":"Soft Matter"},{"key":"2026090315291757000_cit15","first-page":"31","article-title":"Phenylketonuria: An Inborn Error\nof Phenylalanine Metabolism","volume":"29","author":"Williams","year":"2008","journal-title":"Clin. Biochem.\nRev"},{"key":"2026090315291757000_cit16","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/s0005-2736(01)00462-x","article-title":"Differential\nDestabilization of Membranes\nby Tryptophan and Phenylalanine during Freezing: The Roles of Lipid\nComposition and Membrane Fusion","volume":"1561","author":"Popova","year":"2002","journal-title":"Biochim. Biophys.\nActa"},{"key":"2026090315291757000_cit17","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1021\/la010542+","article-title":"Self-Assembly\nof l-Tryptophan on\nthe Cu(001) Surface","volume":"18","author":"Zhao","year":"2002","journal-title":"Langmuir"},{"key":"2026090315291757000_cit18","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1203\/00006450-197608000-00005","article-title":"A Defect in Tryptophan\nMetabolism","volume":"10","author":"Wong","year":"1976","journal-title":"Pediatr. Res"},{"issue":"8","key":"2026090315291757000_cit19","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1107\/S090744499900726X","article-title":"Packing of\nAromatic Rings against Tryptophan Residues\nin Proteins","volume":"55","author":"Samanta","year":"1999","journal-title":"Acta Crystallogr., Sect. D"},{"key":"2026090315291757000_cit20","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.ijbiomac.2020.03.064","article-title":"Role of Aromatic Amino Acids in Amyloid\nSelf-Assembly","volume":"156","author":"Stankovic\u0301","year":"2020","journal-title":"Int. J. Biol. Macromol"},{"issue":"2","key":"2026090315291757000_cit21","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1021\/acsnano.9b07307","article-title":"Self-Assembly\nof Aromatic Amino Acid Enantiomers into Supramolecular Materials of\nHigh Rigidity","volume":"14","author":"Bera","year":"2020","journal-title":"ACS Nano"},{"key":"2026090315291757000_cit22","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1021\/acs.jpcb.2c07607","article-title":"Illustrating the Effect\nof Small Molecules Derived from Natural Resources\non Amyloid Peptides","volume":"127","author":"Roy","year":"2023","journal-title":"J. Phys. Chem. B"},{"key":"2026090315291757000_cit23","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1021\/acschemneuro.1c00104","article-title":"From Small\nMolecules\nto Synthesized Polymers: Potential Role in Combating Amyloidogenic\nDisorders","volume":"12","author":"Ghosh","year":"2021","journal-title":"ACS Chem. Neurosci"},{"issue":"82","key":"2026090315291757000_cit24","doi-asserted-by":"publisher","first-page":"78548","DOI":"10.1039\/C6RA17602J","article-title":"The Role of\nCaffeine as an Inhibitor in the Aggregation of Amyloid Forming Peptides:\nA Unified Molecular Dynamics Simulation and Experimental Study","volume":"6","author":"Sharma","year":"2016","journal-title":"RSC Adv"},{"key":"2026090315291757000_cit25","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.3390\/molecules27082483","article-title":"Molecular Dynamics\nSimulation Studies on the Aggregation\nof Amyloid-\u03b2 Peptides and Their Disaggregation by Ultrasonic\nWave and Infrared Laser Irradiation","volume":"27","author":"Okumura","year":"2022","journal-title":"Molecules"},{"key":"2026090315291757000_cit26","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1007\/s00018-018-2872-2","article-title":"Inhibition of Protein Misfolding\nand Aggregation by\nNatural Phenolic Compounds","volume":"75","author":"Dhouafli","year":"2018","journal-title":"Cell. Mol. Life\nSci"},{"issue":"24","key":"2026090315291757000_cit27","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.1021\/acschemneuro.0c00598","article-title":"Epigallocatechin Gallate Destabilizes\n\u03b1-Synuclein Fibril by Disrupting the E46-K80 Salt-Bridge and\nInter-Protofibril Interface","volume":"11","author":"Yao","year":"2020","journal-title":"ACS Chem. Neurosci"},{"key":"2026090315291757000_cit28","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.1021\/acschemneuro.0c00381","article-title":"Potential Role of Natural\nPolyphenols against Protein Aggregation Toxicity: In Vitro, in Vivo,\nand Clinical Studies","volume":"11","author":"Narayan","year":"2020","journal-title":"ACS Chem. Neurosci"},{"key":"2026090315291757000_cit29","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s12551-019-00606-2","article-title":"Recent Advances\nin the Design and\nApplications of Amyloid-\u03b2 Peptide Aggregation Inhibitors for\nAlzheimer\u2019s Disease Therapy","volume":"11","author":"Jokar","year":"2019","journal-title":"Biophy.Rev"},{"issue":"24","key":"2026090315291757000_cit30","doi-asserted-by":"publisher","first-page":"17579","DOI":"10.1074\/jbc.M112.434787","article-title":"Blood-Brain Barrier(BBB) Disrupter Is Also a Potent\n\u03b1-Synuclein (\u03b1-Syn) Aggregation Inhibitor: A Novel Dual\nMechanism of Mannitol for the Treatment of Parkinson Disease (PD)","volume":"288","author":"Shaltiel-Karyo","year":"2013","journal-title":"J. Biol. Chem"},{"issue":"3","key":"2026090315291757000_cit31","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1021\/acschemneuro.8b00537","article-title":"Norepinephrine Inhibits\nAlzheimer\u2019s Amyloid-\u03b2 Peptide\nAggregation and Destabilizes Amyloid-\u03b2 Protofibrils: A Molecular\nDynamics Simulation Study","volume":"10","author":"Zou","year":"2019","journal-title":"ACS Chem. Neurosci"},{"issue":"1","key":"2026090315291757000_cit32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1039\/C9CP04610K","article-title":"Critical Nucleus\nof Greek-Key-like Core of \u03b1-Synuclein Protofibril\nand Its Disruption by Dopamine and Norepinephrine","volume":"22","author":"Zou","year":"2020","journal-title":"Phys. Chem. Chem. Phys"},{"key":"2026090315291757000_cit33","doi-asserted-by":"publisher","first-page":"8286","DOI":"10.1021\/acsabm.0c01234","article-title":"Introduction\nand Fundamentals\nof Human Islet Amyloid Polypeptide Inhibitors","volume":"3","author":"Tang","year":"2020","journal-title":"ACS Applied Bio Material"},{"key":"2026090315291757000_cit34","doi-asserted-by":"publisher","first-page":"112197","DOI":"10.1016\/j.ejmech.2020.112197","article-title":"Non-Polyphenolic Natural Inhibitors of Amyloid Aggregation","volume":"192","author":"Ma","year":"2020","journal-title":"Eur. J. Med. Chem"},{"issue":"4","key":"2026090315291757000_cit35","doi-asserted-by":"publisher","first-page":"101005","DOI":"10.1016\/j.isci.2020.101005","article-title":"Antioxidant\nBerberine-Derivative Inhibits Multifaceted Amyloid Toxicity","volume":"23","author":"Rajasekhar","year":"2020","journal-title":"iScience"},{"issue":"4","key":"2026090315291757000_cit36","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1021\/acschemneuro.1c00038","article-title":"Serotonin and Melatonin\nShow Different Modes of Action on A\u03b242Protofibril\nDestabilization","volume":"12","author":"Gong","year":"2021","journal-title":"ACS Chem. Neurosci"},{"key":"2026090315291757000_cit37","doi-asserted-by":"publisher","first-page":"140853","DOI":"10.1016\/j.bbapap.2022.140853","article-title":"Polyol and\nSugar Osmolytes Stabilize the Molten Globule State of \u03b1-Lactalbumin\nand Inhibit Amyloid Fibril Formation","volume":"1870","author":"Rahamtullah","year":"2022","journal-title":"Biochim.\nBiophys. Acta, Proteins Proteom"},{"issue":"10","key":"2026090315291757000_cit38","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.bbapap.2018.07.003","article-title":"Effect of Polyols on\nthe Structure and Aggregation of Recombinant\nHuman \u03b3-Synuclein, an Intrinsically Disordered Protein","volume":"1866","author":"Roy","year":"2018","journal-title":"Biochim. Biophys. Acta, Proteins Proteom"},{"key":"2026090315291757000_cit39","doi-asserted-by":"publisher","first-page":"3875","DOI":"10.1038\/srep03875","article-title":"Therapeutic\nImplication of L-Phenylalanine Aggregation Mechanism and Its Modulation\nby D-Phenylalanine in Phenylketonuria","volume":"4","author":"Singh","year":"2014","journal-title":"Sci.\nRep"},{"issue":"6","key":"2026090315291757000_cit40","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1021\/jp309066p","article-title":"Methylations of Tryptophan-Modified Naphthoquinone\nAffect Its Inhibitory Potential toward A\u03b2 Aggregation","volume":"117","author":"Scherzer-Attali","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"2026090315291757000_cit41","doi-asserted-by":"publisher","first-page":"115660","DOI":"10.1016\/j.jphotochem.2024.115660","article-title":"Inhibition of Amyloid\nFibrillation of Single Amino\nAcid Tryptophan by Tannic Acid: An Insight into Targeted Therapy of\nHypertryptophanemia Disorder","volume":"453","author":"Nandy","year":"2024","journal-title":"J. Photochem.\nPhotobiol., A"},{"key":"2026090315291757000_cit42","doi-asserted-by":"publisher","first-page":"150635","DOI":"10.1016\/j.bbrc.2024.150635","article-title":"Tannic Acid: A Possible Therapeutic Agent for Hypermethioninemia-Induced\nNeurochemical Changes in Young Rats","volume":"734","author":"de Moraes Meine","year":"2024","journal-title":"Biochem.\nBiophys. Res. Commun"},{"issue":"11\u201312","key":"2026090315291757000_cit43","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1007\/s00726-020-02913-5","article-title":"Ameliorative Effect of Tannic Acid\non Hypermethioninemia-Induced Oxidative and Nitrosative Damage in\nRats: Biochemical-Based Evidences in Liver, Kidney, Brain, and Serum","volume":"52","author":"de Moraes Meine","year":"2020","journal-title":"Amino Acids"},{"key":"2026090315291757000_cit44","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1747-0285.2005.00318.x","article-title":"Inhibition of Amyloid Fibril Formation\nby Polyphenols: Structural Similarity and Aromatic Interactions as\na Common Inhibition Mechanism","volume":"67","author":"Porat","year":"2006","journal-title":"Chem. Biol. Drug\nDes"},{"issue":"22","key":"2026090315291757000_cit45","doi-asserted-by":"publisher","first-page":"4051","DOI":"10.1021\/acschemneuro.3c00586","article-title":"Understanding the\nMolecular Mechanisms of Polyphenol\nInhibition of Amyloid \u03b2 Aggregation","volume":"14","author":"Han","year":"2023","journal-title":"ACS\nChem. Neurosci"},{"issue":"1","key":"2026090315291757000_cit46","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s42004-018-0025-z","article-title":"Differential Inhibition\nof Metabolite Amyloid Formation by Generic Fibrillation-Modifying\nPolyphenols","volume":"1","author":"Shaham-Niv","year":"2018","journal-title":"Commun. Chem"},{"key":"2026090315291757000_cit47","doi-asserted-by":"publisher","first-page":"8658","DOI":"10.1039\/D5FO03331D","article-title":"Olive Polyphenols\nas Modulators of Amyloid Aggregation: Mechanisms and Implications\nfor Neurodegenerative Diseases","volume":"16","author":"Can\u0303uelo","year":"2025","journal-title":"Food Funct"},{"issue":"35","key":"2026090315291757000_cit48","doi-asserted-by":"publisher","first-page":"9427","DOI":"10.1039\/D3SC02350H","article-title":"A Natural\nPolyphenol Activates and Enhances GPX4 to Mitigate Amyloid-\u03b2\nInduced Ferroptosis in Alzheimer\u2019s Disease","volume":"14","author":"Baruah","year":"2023","journal-title":"Chem. Sci"},{"key":"2026090315291757000_cit49","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1007\/BF02143805","article-title":"The Role\nof Polyols in the Pathophysiology of Hypergalactosemia","volume":"154","author":"Berry","year":"1995","journal-title":"Eur. J. Pediatr"},{"issue":"SUPPL. 1","key":"2026090315291757000_cit50","doi-asserted-by":"publisher","first-page":"D344","DOI":"10.1093\/nar\/gkm791","article-title":"ChEBI: A Database\nand Ontology for Chemical Entities\nof Biological Interest","volume":"36","author":"Degtyarenko","year":"2008","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"2026090315291757000_cit51","doi-asserted-by":"publisher","first-page":"6081","DOI":"10.1063\/1.460447","article-title":"A Complete Basis\nSet Model Chemistry. II. Open-Shell\nSystems and the Total Energies of the First-Row Atoms","volume":"94","author":"Petersson","year":"1991","journal-title":"J. Chem. Phys"},{"key":"2026090315291757000_cit52","unstructured":"Frisch, M.; Trucks, G.; Schlegel, H. B.; Scuseria, G.; Robb, M.; Cheeseman, J.; Scalmani, G.; Barone, V.; Petersson, G.; Nakatsuji, H.; et al., Gaussian\n16; Gaussian, Inc.: Wallingford, CT, 2016."},{"issue":"9","key":"2026090315291757000_cit53","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development\nand Testing of a General Amber Force Field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem"},{"issue":"12","key":"2026090315291757000_cit54","doi-asserted-by":"publisher","first-page":"5146","DOI":"10.1021\/cg100906s","article-title":"Comparative Study\nof Force Fields for Molecular Dynamics\nSimulations of \u03b1-Glycine Crystal Growth from Solution","volume":"10","author":"Cheong","year":"2010","journal-title":"Cryst. Growth Des"},{"issue":"25","key":"2026090315291757000_cit55","doi-asserted-by":"publisher","first-page":"4711","DOI":"10.1021\/acs.jpcb.2c01975","article-title":"Molecular\nDynamics Investigation of Clustering in Aqueous Glycine Solutions","volume":"126","author":"Sweatman","year":"2022","journal-title":"J. Phys. Chem. B"},{"issue":"44","key":"2026090315291757000_cit56","doi-asserted-by":"publisher","first-page":"10799","DOI":"10.1021\/acs.jpcb.4c04798","article-title":"Modulating\nthe Self-Assembly of a Camptothecin Prodrug\nwith Paclitaxel for Anticancer Combination Therapy: A Molecular Dynamics\nApproach","volume":"128","author":"Mitra","year":"2024","journal-title":"J. Phys. Chem. B"},{"issue":"40","key":"2026090315291757000_cit57","doi-asserted-by":"publisher","first-page":"10269","DOI":"10.1021\/j100142a004","article-title":"A Well-Behaved Electrostatic\nPotential Based Method Using Charge Restraints for Deriving Atomic\nCharges: The RESP Model","volume":"97","author":"Bayly","year":"1993","journal-title":"J. Phys. Chem"},{"issue":"1\u20133","key":"2026090315291757000_cit58","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.chemphys.2007.06.043","article-title":"Are Water Simulation Models Consistent\nwith Steady-State and Ultrafast Vibrational Spectroscopy Experiments?","volume":"341","author":"Schmidt","year":"2007","journal-title":"Chem. Phys"},{"key":"2026090315291757000_cit59","doi-asserted-by":"publisher","first-page":"8043","DOI":"10.1021\/acs.chemmater.0c01891","article-title":"Closing the\nGap between Modeling\nand Experiments in the Self-Assembly of Biomolecules at Interfaces\nand in Solution \u2020","volume":"32","author":"Sampath","year":"2020","journal-title":"Chem. Mater"},{"issue":"7","key":"2026090315291757000_cit60","doi-asserted-by":"publisher","first-page":"074501","DOI":"10.1063\/1.4960175","article-title":"Accuracy Limit of\nRigid 3-Point Water Models","volume":"145","author":"Izadi","year":"2016","journal-title":"J. Chem. Phys"},{"issue":"11","key":"2026090315291757000_cit61","doi-asserted-by":"publisher","first-page":"3569","DOI":"10.1021\/ct1003687","article-title":"Explicit Water Models\nAffect the Specific Solvation and Dynamics of Unfolded Peptides While\nthe Conformational Behavior and Flexibility of Folded Peptides Remain\nIntact","volume":"6","author":"Florova\u0301","year":"2010","journal-title":"J. Chem. Theory Comput"},{"issue":"1","key":"2026090315291757000_cit62","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1021\/acs.jctc.1c00257","article-title":"How the Choice of Force-Field Affects\nthe Stability and Self-Assembly Process of Supramolecular CTA Fibers","volume":"18","author":"Piskorz","year":"2022","journal-title":"J. Chem. Theory Comput"},{"key":"2026090315291757000_cit63","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS:\nFast, Flexible, and Free","volume":"26","author":"Van","year":"2005","journal-title":"J. Comput. Chem"},{"issue":"13","key":"2026090315291757000_cit64","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1002\/jcc.21224","article-title":"PACKMOL:\nA Package for Building Initial Configurations for Molecular Dynamics\nSimulations","volume":"30","author":"Martinez","year":"2009","journal-title":"J. Comput. Chem"},{"issue":"1","key":"2026090315291757000_cit65","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"},{"issue":"12","key":"2026090315291757000_cit66","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic Transitions in Single Crystals: A New Molecular\nDynamics Method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys"},{"issue":"19","key":"2026090315291757000_cit67","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A Smooth Particle\nMesh Ewald Method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys"},{"issue":"12","key":"2026090315291757000_cit68","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12&lt;1463::AID-JCC4&gt;3.0.CO;2-H","article-title":"LINCS: A Linear\nConstraint Solver for Molecular Simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem"},{"issue":"10","key":"2026090315291757000_cit69","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1002\/jcc.21787","article-title":"MDAnalysis:\nA Toolkit for the Analysis of Molecular Dynamics Simulations","volume":"32","author":"Michaud-Agrawal","year":"2011","journal-title":"J. Comput. Chem"},{"issue":"9","key":"2026090315291757000_cit70","doi-asserted-by":"publisher","first-page":"4151","DOI":"10.1021\/acschemneuro.9b00393","article-title":"Molecular Dynamics\nSimulations Reveal the Inhibitory Mechanism of Dopamine against Human\nIslet Amyloid Polypeptide (HIAPP) Aggregation and Its Destabilization\nEffect on HIAPP Protofibrils","volume":"10","author":"Lao","year":"2019","journal-title":"ACS Chem. Neurosci"},{"issue":"49","key":"2026090315291757000_cit71","doi-asserted-by":"publisher","first-page":"10427","DOI":"10.1021\/acs.jpcb.2c05970","article-title":"Disparate\nEffect of Hybrid Peptidomimetics Containing Isomers of\nAminobenzoic Acid on HIAPP Aggregation","volume":"126","author":"Roy","year":"2022","journal-title":"J. Phys.\nChem. B"},{"issue":"17","key":"2026090315291757000_cit72","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.1021\/acschemneuro.4c00387","article-title":"Comprehending the Efficacy of Whitlock\u2019s\nCaffeine-Pincered\nMolecular Tweezer on \u03b2-Amyloid Aggregation","volume":"15","author":"Devi","year":"2024","journal-title":"ACS Chem. Neurosci"},{"issue":"1","key":"2026090315291757000_cit73","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1039\/C1CE05763D","article-title":"A Simple and Robust\nMethod for the Identification of\n\u03c0-\u03c0 Packing Motifs of Aromatic Compounds","volume":"14","author":"Loots","year":"2012","journal-title":"CrystEngcomm"},{"issue":"4","key":"2026090315291757000_cit75","doi-asserted-by":"publisher","first-page":"331","DOI":"10.4208\/cicc.2025.146.01","article-title":"Breathing New Life\ninto Classical Force Fields","volume":"7","author":"Sun","year":"2025","journal-title":"Commun. Comput.\nChem"},{"issue":"14","key":"2026090315291757000_cit76","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1002\/jcc.21226","article-title":"Assessment\nof Standard Force Field\nModels against High-Quality Ab Initio Potential Curves for Prototypes\nof \u03c0-\u03c0, CH\/\u03c0, and SH\/\u03c0 Interactions","volume":"30","author":"Sherrill","year":"2009","journal-title":"J. Comput. Chem"},{"key":"2026090315291757000_cit77","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1103\/PhysRevLett.85.768","article-title":"Effects of\nIon Atmosphere on Hydrogen-Bond Dynamics in Aqueous Electrolyte Solutions","volume":"85","author":"Chandra","year":"2000","journal-title":"Phys. Rev. Lett."},{"issue":"19","key":"2026090315291757000_cit78","doi-asserted-by":"publisher","first-page":"9674","DOI":"10.1021\/jp057544d","article-title":"Dynamics of Halide\nIon-Water Hydrogen Bonds in Aqueous\nSolutions: Dependence on Ion Size and Temperature","volume":"110","author":"Chowdhuri","year":"2006","journal-title":"J. Phys. Chem. B"},{"issue":"16","key":"2026090315291757000_cit79","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1021\/jp022147d","article-title":"Dynamical\nBehavior of Anion\u2013Water and Water\u2013Water Hydrogen Bonds\nin Aqueous Electrolyte Solutions: A Molecular Dynamics Study","volume":"107","author":"Chandra","year":"2003","journal-title":"J. Phys. Chem. B"},{"issue":"6","key":"2026090315291757000_cit80","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.1016\/S0006-3495(00)76533-7","article-title":"Residence Times\nof Water Molecules in the Hydration Sites of Myoglobin","volume":"79","author":"Makarov","year":"2000","journal-title":"Biophys. J"},{"issue":"5","key":"2026090315291757000_cit81","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1021\/bm2001507","article-title":"Heterogeneous Triangular Structures\nof Human Islet Amyloid Polypeptide (Amylin) with Internal Hydrophobic\nCavity and External Wrapping Morphology Reveal the Polymorphic Nature\nof Amyloid Fibrils","volume":"12","author":"Zhao","year":"2011","journal-title":"Biomacromolecules"},{"key":"2026090315291757000_cit82","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/0021-9991(77)90121-8","article-title":"Nonphysical\nSampling Distributions in Monte Carlo Free-Energy\nEstimation; Umbrella Sampling","volume":"23","author":"Torrie","year":"1977","journal-title":"J. Comput. Phys."},{"key":"2026090315291757000_cit83","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1002\/wcms.66","article-title":"Umbrella Sampling","volume":"1","author":"Ka\u0308stner","year":"2011","journal-title":"Wiley Interdiscip. Rev.: Comput. Mol. Sci"},{"key":"2026090315291757000_cit84","doi-asserted-by":"publisher","first-page":"342","DOI":"10.2174\/157489312803901009","article-title":"Steered Molecular Dynamics-$ Promising Tool for Drug\nDesign","volume":"7","author":"Suan Li","year":"2012","journal-title":"Curr. Bioinform."},{"issue":"6","key":"2026090315291757000_cit85","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.jbbm.2007.10.006","article-title":"A Steered Molecular Dynamics Method\nwith Direction Optimization and Its Applications on Ligand Molecule\nDissociation","volume":"70","author":"Liu","year":"2008","journal-title":"J. Biochem Biophys. Methods"},{"key":"2026090315291757000_cit86","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"Gromacs: High Performance\nMolecular Simulations through Multi-Level Parallelism from Laptops\nto Supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"2026090315291757000_cit87","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/jcc.540130812","article-title":"Weighted\nHistogram Analysis Method for Free-Energy Calculations on Biomolecules.\nI. The Method","volume":"13","author":"Kumar","year":"1992","journal-title":"J. Comput. Chem."},{"key":"2026090315291757000_cit88","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/S0010-4655(00)00215-0","article-title":"Extension to the Weighted Histogram\nAnalysis Method: Combining Umbrella\nSampling with Free Energy Calculations","volume":"135","author":"Souaille","year":"2001","journal-title":"Comput.\nPhys. Commun."},{"issue":"28","key":"2026090315291757000_cit89","doi-asserted-by":"publisher","first-page":"17141","DOI":"10.1021\/acsomega.0c01020","article-title":"Structure and Morphology\nof Indole Analogue Crystals","volume":"5","author":"Pisarek","year":"2020","journal-title":"ACS Omega"},{"issue":"14","key":"2026090315291757000_cit90","doi-asserted-by":"publisher","first-page":"6092","DOI":"10.1021\/jacs.9b02046","article-title":"Supramolecular Polymorphism in One-Dimensional\nSelf-Assembly by Kinetic Pathway Control","volume":"141","author":"Wehner","year":"2019","journal-title":"J.\nAm. Chem. Soc"},{"issue":"12","key":"2026090315291757000_cit91","doi-asserted-by":"publisher","first-page":"3713","DOI":"10.1021\/ct100494z","article-title":"G-Whams-a Free Weighted Histogram\nAnalysis Implementation Including Robust Error and Autocorrelation\nEstimates","volume":"6","author":"Hub","year":"2010","journal-title":"J. Chem. Theory Comput"}],"container-title":["The Journal of Physical\nChemistry B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpcb.6c03238","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/35\/8794\/67329816\/acs.jpcb.6c03238.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/35\/8794\/67329816\/acs.jpcb.6c03238.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:29:30Z","timestamp":1788463770000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article\/130\/35\/8794\/5321876\/Mechanistic-Role-of-Different-Functional-Groups-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":90,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2026,8,24]]},"published-print":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpcb.6c03238","relation":{},"ISSN":["1520-6106","1520-5207"],"issn-type":[{"value":"1520-6106","type":"print"},{"value":"1520-5207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}