{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:07:55Z","timestamp":1790176075379,"version":"4.1.0"},"reference-count":56,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["142429"],"award-info":[{"award-number":["142429"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Understanding the molecular-level hydration of fructose tautomers remains a challenge due to their rapid interconversion and structural complexity. A dual-scale approach was employed, combining long-time classical molecular dynamics (MD) and ab initio molecular dynamics (AIMD) to elucidate differences in the hydrogen-bonding networks of both pyranose and furanose tautomers with statistical and electronic accuracy. Our simulations highlight the inherent competition between intra- and intermolecular hydrogen bonds, driven by the limited number of hydroxyl donor and acceptor sites. Crucially, the formation of these internal bonds is driven by ring puckering in the flexible furanoses alongside the spatial orientation of the hydroxymethyl groups in both tautomer families. This structural interplay indirectly influences the entire intermolecular solvation shell, comprising both hydrophilic and hydrophobic regions. By correlating these competing intra- and intermolecular patterns with Bader charges and water dipole moments, we establish a quantitative electronic-structure basis for carbohydrate solvation. These insights provide a comprehensive atomistic framework that deepens our understanding of biologically relevant processes, such as recognition and docking efficiency within metabolic enzymes.<\/jats:p>","DOI":"10.1021\/acsphyschemau.6c00122","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:01:49Z","timestamp":1788850909000},"page":"1372-1386","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling\nthe Complex Hydrogen-Bonding and Solvation\nPatterns of Fructose Tautomers via Complementary AIMD and Classical\nMD Simulations"],"prefix":"10.1021","volume":"6","author":[{"given":"Imre","family":"Bako\u0301","sequence":"first","affiliation":[{"name":"HUN-REN Research Centre for Natural Sciences , Magyar tudo\u0301sok ko\u0308ru\u0301tja 2 , ,","place":["Budapest, Hungary, H-1117"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-1813","authenticated-orcid":true,"given":"Szilvia","family":"Pothoczki","sequence":"additional","affiliation":[{"name":"HUN-REN Wigner Research Centre for Physics , Konkoly-Thege M. U\u0301t 29-33 , ,","place":["Budapest, Hungary, H-1121"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"5","key":"2026092310081229500_cit1","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1021\/acschembio.2c00682","article-title":"Discrimination of GLUTs by Fructose Isomers Enables\nSimultaneous Screening of GLUT5 and GLUT2 Activity in Live Cells","volume":"18","author":"Gora","year":"2023","journal-title":"ACS Chem. Biol."},{"issue":"2","key":"2026092310081229500_cit2","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1021\/cr940283b","article-title":"Glycobiology:\nToward Understanding the Function of Sugars","volume":"96","author":"Dwek","year":"1996","journal-title":"Chem. Rev."},{"issue":"1","key":"2026092310081229500_cit3","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.carres.2011.11.003","article-title":"Observation\nof the Keto Tautomer of d-Fructose in D2O Using 1H NMR Spectroscopy","volume":"347","author":"Barclay","year":"2012","journal-title":"Carbohydr. Res."},{"issue":"1","key":"2026092310081229500_cit4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0308-8146(84)90024-4","article-title":"Relationship\nBetween the Structure and the Properties of Carbohydrates in Aqueous\nSolutions: Solute\u2013Solvent Interactions and the Sweetness of d-Fructose, d-Glucose and Sucrose in Solution","volume":"13","author":"Mathlouthi","year":"1984","journal-title":"Food Chem."},{"key":"2026092310081229500_cit5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0065-2318(08)60122-5","article-title":"The Composition\nof Reducing Sugars in Solution","volume":"42","author":"Angyal","year":"1984","journal-title":"Adv. Carbohydr.\nChem. Biochem."},{"issue":"4","key":"2026092310081229500_cit6","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s10858-016-0028-y","article-title":"Insights into Furanose Solution Conformations:\nBeyond\nthe Two-State Model","volume":"64","author":"Wang","year":"2016","journal-title":"J. Biomol. NMR"},{"issue":"23","key":"2026092310081229500_cit7","doi-asserted-by":"publisher","first-page":"8205","DOI":"10.1021\/ja00778a043","article-title":"Conformational\nAnalysis of the Sugar Ring in Nucleosides\nand Nucleotides. New Description Using the Concept of Pseudorotation","volume":"94","author":"Altona","year":"1972","journal-title":"J. Am. Chem. Soc."},{"issue":"3","key":"2026092310081229500_cit8","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1021\/cr300249c","article-title":"Conformational\nAnalysis of Furanoside-Containing\nMono- and Oligosaccharides","volume":"113","author":"Taha","year":"2013","journal-title":"Chem. Rev."},{"issue":"36","key":"2026092310081229500_cit9","doi-asserted-by":"publisher","first-page":"7925","DOI":"10.1021\/jp505719m","article-title":"Cyclic and\nAcyclic Fructose Conformers in the Gas Phase: A Large-Scale\nSecond-Order Perturbation Theory Study","volume":"118","author":"Szczepaniak","year":"2014","journal-title":"J. Phys.\nChem. A"},{"key":"2026092310081229500_cit10","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nature14909","article-title":"Structure\nand mechanism of the mammalian fructose transporter GLUT5","volume":"526","author":"Nomura","year":"2015","journal-title":"Nature"},{"issue":"5","key":"2026092310081229500_cit11","doi-asserted-by":"publisher","first-page":"5189","DOI":"10.1021\/jacs.5c17290","article-title":"Atomistic Insights\ninto Anomeric and Stereochemical Effects on Glucose Transport by GLUTs","volume":"148","author":"Wiley","year":"2026","journal-title":"J. Am. Chem. Soc."},{"issue":"42","key":"2026092310081229500_cit12","doi-asserted-by":"publisher","first-page":"38376","DOI":"10.1021\/jacs.5c11504","article-title":"Shaping the Glycan\nLandscape: Hidden Relationships between Linkage and Ring Distortions\nInduced by Carbohydrate-Active Enzymes","volume":"147","author":"Grothaus","year":"2025","journal-title":"J. Am.\nChem. Soc."},{"issue":"19","key":"2026092310081229500_cit13","doi-asserted-by":"publisher","first-page":"10541","DOI":"10.1073\/pnas.191362798","article-title":"Solvent Interactions Determine Carbohydrate Conformation","volume":"98","author":"Kirschner","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"2","key":"2026092310081229500_cit14","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/S0008-6215(00)86024-3","article-title":"X-ray Diffraction\nStudy of the Molecular Association in Aqueous Solutions of d-Fructose, d-Glucose, and Sucrose","volume":"91","author":"Mathlouthi","year":"1981","journal-title":"Carbohydr. Res."},{"issue":"13","key":"2026092310081229500_cit15","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1021\/acs.jpclett.8b01280","article-title":"Hydrogen Bond Length as a Key To\nUnderstanding Sweetness","volume":"9","author":"Bruni","year":"2018","journal-title":"J. Phys. Chem. Lett."},{"key":"2026092310081229500_cit16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.carres.2015.01.002","article-title":"Quantitative Characterization of Hydration State and Destructuring\nEffect of Monosaccharides and Disaccharides on Water Hydrogen Bond\nNetwork","volume":"406","author":"Shiraga","year":"2015","journal-title":"Carbohydr. Res."},{"issue":"10","key":"2026092310081229500_cit17","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1021\/jp0030084","article-title":"Molecular Dynamics\nof Carbohydrate Aqueous Solutions:\nDielectric Relaxation as a Function of Glucose and Fructose Concentration","volume":"105","author":"Fuchs","year":"2001","journal-title":"J. Phys. Chem. B"},{"key":"2026092310081229500_cit18","doi-asserted-by":"publisher","first-page":"112516","DOI":"10.1016\/j.jfoodeng.2025.112516","article-title":"Investigating the Behavior of d-Glucose, d-Fructose, and d-Allulose in Aqueous\nMedia by Molecular Dynamics Simulations","volume":"394","author":"Bug\u0306day","year":"2025","journal-title":"J.\nFood Eng."},{"key":"2026092310081229500_cit19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3126\/hp.v9i01.40153","article-title":"Diffusion of fructose\nin water: a molecular dynamics\nstudy","volume":"9","author":"Bhusal","year":"2021","journal-title":"Himalayan Phys."},{"issue":"39","key":"2026092310081229500_cit20","doi-asserted-by":"publisher","first-page":"12999","DOI":"10.1021\/jp904019c","article-title":"Anomalous Dynamics\nof Hydration Water in Carbohydrate Solutions","volume":"113","author":"Pomata","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"2026092310081229500_cit21","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.comptc.2015.11.011","article-title":"Quantum Chemical\nStudy of Dissociative\nElectron Attachment to d-Ribose and d-Fructose","volume":"1075","author":"Fujita","year":"2016","journal-title":"Comput. Theor. Chem."},{"issue":"4","key":"2026092310081229500_cit22","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1016\/j.foodchem.2007.02.047","article-title":"Relationships\nbetween Hydration Number, Water Activity and Density of Aqueous Sugar\nSolutions","volume":"106","author":"Gharsallaoui","year":"2008","journal-title":"Food Chem."},{"issue":"18","key":"2026092310081229500_cit23","doi-asserted-by":"publisher","first-page":"20331","DOI":"10.1021\/acsomega.4c00798","article-title":"Outstanding\nProperties of the Hydration\nShell around \u03b2-d-Glucose: A Computational Study","volume":"9","author":"Bako\u0301","year":"2024","journal-title":"ACS Omega"},{"key":"2026092310081229500_cit24","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.carres.2017.04.019","article-title":"Hydrophobicity\nof Carbohydrates and Related Hydroxy Compounds","volume":"446\u2013447","author":"Buttersack","year":"2017","journal-title":"Carbohydr. Res."},{"issue":"13","key":"2026092310081229500_cit25","doi-asserted-by":"publisher","first-page":"5321","DOI":"10.1021\/j100166a073","article-title":"Stereochemical aspects of hydration\nof carbohydrates\nin aqueous solutions. 3. Density and ultrasound measurements","volume":"95","author":"Galema","year":"1991","journal-title":"J. Phys. Chem."},{"issue":"50","key":"2026092310081229500_cit26","doi-asserted-by":"publisher","first-page":"24152","DOI":"10.1021\/jp0543072","article-title":"Carbohydrate\nIntramolecular Hydrogen\nBonding Cooperativity and Its Effect on Water Structure","volume":"109","author":"Dashnau","year":"2005","journal-title":"J. Phys. Chem. B"},{"issue":"9","key":"2026092310081229500_cit27","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1021\/cr020661","article-title":"Water Dynamics\nin the Hydration Layer around Proteins and Micelles","volume":"105","author":"Bagchi","year":"2005","journal-title":"Chem. Rev."},{"issue":"9","key":"2026092310081229500_cit28","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1039\/C9OB00043G","article-title":"The Systematic Influence of Solvent on the Conformational\nFeatures of Furanosides","volume":"17","author":"Gaweda","year":"2019","journal-title":"Org. Biomol. Chem."},{"issue":"1","key":"2026092310081229500_cit29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1214\/aos\/1176344552","article-title":"Bootstrap\nMethods: Another Look at the Jackknife","volume":"7","author":"Efron","year":"1979","journal-title":"Ann.\nStat."},{"issue":"2","key":"2026092310081229500_cit30","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1214\/ss\/1063994972","article-title":"The Impact\nof the Bootstrap on Statistical Algorithms and Theory","volume":"18","author":"Beran","year":"2003","journal-title":"Stat. Sci."},{"issue":"3","key":"2026092310081229500_cit31","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.commatsci.2005.04.010","article-title":"A Fast and Robust Algorithm for Bader\nDecomposition of Charge Density","volume":"36","author":"Henkelman","year":"2006","journal-title":"Comput. Mater.\nSci."},{"key":"2026092310081229500_cit32","doi-asserted-by":"publisher","first-page":"111579","DOI":"10.1016\/j.molliq.2019.111579","article-title":"Effects of\nH-Bond Asymmetry on the Electronic Properties of Liquid Water\u2500An\nAIMD Analysis","volume":"293","author":"Bako\u0301","year":"2019","journal-title":"J. Mol. Liq."},{"issue":"24","key":"2026092310081229500_cit33","doi-asserted-by":"publisher","first-page":"5211","DOI":"10.1021\/jp403355e","article-title":"Determination\nof Proton Affinities\nand Acidity Constants of Sugars","volume":"117","author":"Feng","year":"2013","journal-title":"J. Phys. Chem.\nA"},{"issue":"32","key":"2026092310081229500_cit34","doi-asserted-by":"publisher","first-page":"6881","DOI":"10.1021\/acs.jpca.1c04695","article-title":"Following in Emil Fischer\u2019s Footsteps: A Site-Selective\nProbe of Glucose Acid\u2013Base Chemistry","volume":"125","author":"Malerz","year":"2021","journal-title":"J. Phys. Chem. A"},{"issue":"6","key":"2026092310081229500_cit35","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1021\/acs.jchemed.6b00623","article-title":"T. pKa Values in the\nUndergraduate Curriculum: What\nIs the Real pKa of Water?","volume":"94","author":"Silverstein","year":"2017","journal-title":"J. Chem. Educ."},{"issue":"8081","key":"2026092310081229500_cit36","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41586-025-09302-6","article-title":"Structural and Functional Characterization\nof Human Sweet Taste Receptor","volume":"645","author":"Shi","year":"2025","journal-title":"Nature"},{"key":"2026092310081229500_cit37","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":"2026092310081229500_cit38","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1002\/jcc.21004","article-title":"Additive Empirical\nForce Field for Hexopyranose Monosaccharides","volume":"29","author":"Guvench","year":"2008","journal-title":"J. Comput. Chem."},{"issue":"24","key":"2026092310081229500_cit39","doi-asserted-by":"publisher","first-page":"6269","DOI":"10.1021\/j100308a038","article-title":"The Missing Term in Effective Pair\nPotentials","volume":"91","author":"Berendsen","year":"1987","journal-title":"J. Phys. Chem."},{"key":"2026092310081229500_cit40","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."},{"key":"2026092310081229500_cit41","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh\nEwald: An N\u00b7log(N)\nMethod for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem.\nPhys."},{"key":"2026092310081229500_cit42","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular\nDynamics with Coupling to an External Bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J. Chem. Phys."},{"key":"2026092310081229500_cit43","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1080\/00268978400101201","article-title":"A Molecular\nDynamics Method for Simulations in the Canonical Ensemble","volume":"52","author":"Nose\u0301","year":"1984","journal-title":"Mol. Phys."},{"key":"2026092310081229500_cit44","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical\nDynamics: Equilibrium Phase-Space Distributions","volume":"31","author":"Hoover","year":"1985","journal-title":"Phys. Rev. A"},{"key":"2026092310081229500_cit45","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.cpc.2004.12.014","article-title":"Quickstep: Fast and Accurate Density\nFunctional Calculations Using a Mixed Gaussian and Plane Waves Approach","volume":"167","author":"VandeVondele","year":"2005","journal-title":"Comput. Phys. Commun."},{"key":"2026092310081229500_cit46","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/wcms.1159","article-title":"CP2K: Atomistic\nSimulations of Condensed Matter Systems","volume":"4","author":"Hutter","year":"2014","journal-title":"WIREs\nComput. Mol. Sci."},{"key":"2026092310081229500_cit47","unstructured":"The CP2K Developers Group.\n          \n          CP2K, Version\n3.9.0; CP2K Developers Group, http:\/\/www.cp2k.org\/."},{"key":"2026092310081229500_cit48","doi-asserted-by":"publisher","first-page":"A1133","DOI":"10.1103\/PhysRev.140.A1133","article-title":"Self-Consistent Equations Including\nExchange and Correlation\nEffects","volume":"140","author":"Kohn","year":"1965","journal-title":"Phys. Rev."},{"issue":"6","key":"2026092310081229500_cit49","doi-asserted-by":"publisher","first-page":"3098","DOI":"10.1103\/PhysRevA.38.3098","article-title":"Density-Functional\nExchange-Energy Approximation with Correct Asymptotic Behavior","volume":"38","author":"Becke","year":"1988","journal-title":"Phys. Rev. A"},{"issue":"2","key":"2026092310081229500_cit50","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","article-title":"Development\nof the Colle\u2013Salvetti\nCorrelation-Energy Formula into a Functional of the Electron Density","volume":"37","author":"Lee","year":"1988","journal-title":"Phys. Rev. B"},{"issue":"15","key":"2026092310081229500_cit51","doi-asserted-by":"publisher","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A Consistent and Accurate\nAb Initio Parametrization of Density Functional Dispersion Correction\n(DFT-D) for the 94 Elements H\u2013Pu","volume":"132","author":"Grimme","year":"2010","journal-title":"J.\nChem. Phys."},{"issue":"3","key":"2026092310081229500_cit52","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1103\/PhysRevB.54.1703","article-title":"Separable Dual-Space Gaussian Pseudopotentials","volume":"54","author":"Goedecker","year":"1996","journal-title":"Phys. Rev. B"},{"issue":"3","key":"2026092310081229500_cit53","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1080\/002689797170220","article-title":"A Hybrid Gaussian\nand Plane Wave\nDensity Functional Scheme","volume":"92","author":"Lippert","year":"1997","journal-title":"Mol. Phys."},{"issue":"15","key":"2026092310081229500_cit54","doi-asserted-by":"publisher","first-page":"154503","DOI":"10.1063\/1.3651474","article-title":"Van der Waals\neffects in ab initio water at ambient and supercritical conditions","volume":"135","author":"Jonchiere","year":"2011","journal-title":"J. Chem. Phys."},{"key":"2026092310081229500_cit55","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.commatsci.2005.04.010","article-title":"A fast and robust algorithm for Bader\ndecomposition of charge density","volume":"36","author":"Henkelman","year":"2006","journal-title":"Comput. Mater.\nSci."},{"key":"2026092310081229500_cit56","volume-title":"Bader Charge Analysis Code","author":"Henkelman Group."}],"container-title":["ACS Physical Chemistry Au"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsphyschemau.6c00122","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/apcach\/article-pdf\/6\/5\/1372\/68437378\/acsphyschemau.6c00122.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/apcach\/article-pdf\/6\/5\/1372\/68437378\/acsphyschemau.6c00122.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:31:07Z","timestamp":1790173867000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/apcach\/article\/6\/5\/1372\/5425784\/Unraveling-the-Complex-Hydrogen-Bonding-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9,8]]},"published-print":{"date-parts":[[2026,9,23]]}},"URL":"https:\/\/doi.org\/10.1021\/acsphyschemau.6c00122","relation":{},"ISSN":["2694-2445"],"issn-type":[{"value":"2694-2445","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}