Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Generating 3D models of complex carbohydrates with GLYCAM-Web

Nature Methods volume 23, pages 720–723 (2026) Cite this article

Subjects

Abstract

We present online three-dimensional (3D) structure-prediction tools at GLYCAM-Web (www.glycam.org) that can be used for generating experimentally consistent 3D structures of oligosaccharides for data interpretation, hypothesis generation, 3D visualization, molecular docking and further simulation. The tools support the modeling of an unlimited array of natural glycans and polysaccharides, glycosaminoglycans, engineered glycomaterials and glycoproteins. GLYCAM-Web is directly linked to external databases, such as the Protein Data Bank, facilitating comparison with experimental data.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The GLYCAM-Web point-and-click builder.
The alternative text for this image may have been generated using AI.
Fig. 2: GLYCAM-Web reproduces the conformations of experimentally determined carbohydrate 3D structures.
The alternative text for this image may have been generated using AI.

Similar content being viewed by others

Data availability

The data and code used to generate Fig. 2 are available at https://github.com/RajanKandel/PDB_glycosidic_link_study_V2/. The experimental dihedral angle data generated using GlyFinder (v.0.0.1) are available at https://github.com/RajanKandel/PDB_glycosidic_link_study_V2/tree/main/data_gf_query

Code availability

The GEMS (v.0.0.1) and GMML2 (v.1.5.0) software repositories are open-source (GNU Lesser General Public License v.3.0) and publicly accessible on GitHub (https://github.com/GLYCAM-Web). For security reasons, the website code and deployment pipeline have not been made public.

References

  1. Gazaway, E., Kandel, R., Grant, O. C. & Woods, R. J. Are N-linked glycans intrinsically disordered? Curr. Opin. Struct. Biol. 93, 103118 (2025).

    Article  CAS  PubMed  Google Scholar 

  2. Woods, R. J. Predicting the structures of glycans, glycoproteins, and their complexes. Am. Chem. Soc. 118, 8005–8024 (2018).

    CAS  Google Scholar 

  3. Brisson, J.-R. & Carver, J. P. Solution conformation of aD(1-3)- and aD(1-6)-linked oligomannosides using proton nuclear magnetic resonance. Biochemistry 22, 1362–1368 (1983).

    Article  CAS  PubMed  Google Scholar 

  4. Homans, S. W. Conformation and dynamics of oligosaccharides in solution. Glycobiology 3, 551–555 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Weiner, P. K. & Kollman, P. A. AMBER: assisted model building with energy refinement. a general program for modeling molecules and their interactions. J. Comp. Chem. 2, 287–303 (1981).

    Article  CAS  Google Scholar 

  6. Amos, R. A. et al. Polymerization of the backbone of the pectic polysaccharide rhamnogalacturonan I. Nat. Plants 8, 1289–1303 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Purushotham, P. et al. Mechanism of mixed-linkage glucan biosynthesis by barley cellulose synthase-like CslF6 (1,3;1,4)-β-glucan synthase. Sci. Adv. 8, eadd1596 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Klontz, E. H. et al. Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation. Nat. Commun. 11, 6204 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ishida, T., Parks, J. M. & Smith, J. C. Insight into the catalytic mechanism of gh11 xylanase: computational analysis of substrate distortion based on a neutron structure. J. Am. Chem. Soc. 142, 17966–17980 (2020).

    Article  CAS  PubMed  Google Scholar 

  10. Ives, C. M. et al. Restoring protein glycosylation with GlycoShape. Nat. Methods 21, 2117–2127 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schachner, L. F. et al. Exposing the molecular heterogeneity of glycosylated biotherapeutics. Nat. Commun. 15, 3259 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Unione, L., Arda, A., Jimenez-Barbero, J. & Millet, O. NMR of glycoproteins: profiling, structure, conformation and interactions. Curr. Opin. Struct. Biol. 68, 9–17 (2021).

    Article  CAS  PubMed  Google Scholar 

  13. Murphy, P. V. et al. Small lectin ligands as a basis for applications in glycoscience and glycomedicine. Chem. Soc. Rev. 53, 9428–9445 (2024).

    Article  CAS  PubMed  Google Scholar 

  14. Urban, J. et al. Predicting glycan structure from tandem mass spectrometry via deep learning. Nat. Methods 21, 1206–1215 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Widmalm, G. Glycan shape, motions, and interactions explored by NMR spectroscopy. JACS Au. 4, 20–39 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Prestegard, J. H. A consensus structural motif for the capsular polysaccharide of Cryptococcus neoformans by NMR/MD. Proc. Natl Acad. Sci. USA 121, e2322413121 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Day, C. J. et al. The essential malaria protein PfCyRPA targets glycans to invade erythrocytes. Cell Rep. 43, 114012 (2024).

    Article  CAS  PubMed  Google Scholar 

  18. Canales, A. et al. Revealing the specificity of human H1 influenza a viruses to complex N-glycans. JACS Au. 3, 868–878 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pang, Y. T., Acharya, A., Lynch, D. L., Pavlova, A. & Gumbart, J. C. SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact. Commun. Biol. 5, 1170 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brunetti, N. S. et al. SARS-CoV-2 uses CD4 to infect T helper lymphocytes. eLife 12, e84790 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Neelamegham, S. et al. Updates to the symbol nomenclature for glycans guidelines. Glycobiology 29, 620–624 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sehnal, D. et al. Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures. Nucleic Acids Res. 49, W431–W437 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sehnal, D. & Grant, O. C. Rapidly display glycan symbols in 3D structures: 3D-SNFG in LiteMol. J. Proteome Res. 18, 770–774 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Kirschner, K. N. et al. GLYCAM06: a generalizable biomolecular force field. Carbohydrates. J. Comput. Chem. 29, 622–655 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Meredith, R. J., Carmichael, I., Woods, R. J. & Serianni, A. S. MA’AT analysis: probability distributions of molecular torsion angles in solution from NMR spectroscopy. Acc. Chem. Res. 56, 2313–2328 (2023).

    Article  CAS  PubMed  Google Scholar 

  26. Shao, C. et al. Modernized uniform representation of carbohydrate molecules in the Protein Data Bank. Glycobiology 31, 1204–1218 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235–242 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Agirre, J., Davies, G., Wilson, K. & Cowtan, K. Carbohydrate anomalies in the PDB. Nat. Chem. Biol. 11, 303 (2015).

    Article  CAS  PubMed  Google Scholar 

  29. Tsuchiya, S., Yamada, I. & Aoki-Kinoshita, K. F. GlycanFormatConverter: a conversion tool for translating the complexities of glycans. Bioinformatics 35, 2434–2440 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tanaka, K. et al. WURCS: the Web3 unique representation of carbohydrate structures. J. Chem. Inf. Model. 54, 1558–1566 (2014).

    Article  CAS  PubMed  Google Scholar 

  31. McNaught, A. D. Nomenclature of carbohydrates (recommendations 1996). Adv. Carbohydr. Chem. Biochem. 52, 43–177 (1997).

    CAS  PubMed  Google Scholar 

  32. McNaught, A. D. International Union of Pure and Applied Chemistry and International Union of Biochemistry and Molecular Biology. Joint Commission on Biochemical Nomenclature. Nomenclature of carbohydrates. Carbohydr. Res. 297, 1–92 (1997).

    Article  CAS  PubMed  Google Scholar 

  33. Bernstein, H. J. et al. Specification of the crystallographic information file format, version 2.0. J. Appl. Crystallogr. 49, 277–284 (2016).

    Article  CAS  Google Scholar 

  34. Singh, A., Montgomery, D., Xue, X., Foley, B. L. & Woods, R. J. GAG Builder: a web-tool for modeling 3D structures of glycosaminoglycans. Glycobiology 29, 515–518 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wessels, M. R., Pozsgay, V., Kasper, D. L. & Jennings, H. J. Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B Streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. J. Biol. Chem. 262, 8262–8267 (1987).

    Article  CAS  PubMed  Google Scholar 

  36. Sattelle, B. M., Hansen, S. U., Gardiner, J. & Almond, A. Free energy landscapes of iduronic acid and related monosaccharides. J. Am. Chem. Soc. 132, 13132–13134 (2010).

    Article  CAS  PubMed  Google Scholar 

  37. Jin, L., Hricovini, M., Deakin, J. A., Lyon, M. & Uhrin, D. Residual dipolar coupling investigation of a heparin tetrasaccharide confirms the limited effect of flexibility of the iduronic acid on the molecular shape of heparin. Glycobiology 19, 1185–1196 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Muñoz-García, J. C., Corzana, F., de Paz, J. L., Angulo, J. & Nieto, P. M. Conformations of the iduronate ring in short heparin fragments described by time-averaged distance restrained molecular dynamics. Glycobiology 23, 1220–1229 (2013).

    Article  PubMed  Google Scholar 

  39. Forster, M. J. & Mulloy, B. Molecular-dynamics study of iduronate ring conformation. Biopolymers 33, 575–588 (1993).

    Article  CAS  Google Scholar 

  40. Zhang, W. et al. Conformational populations of β-(1–>4) O-glycosidic linkages using redundant NMR J-couplings and circular statistics. J. Phys. Chem. B 121, 3042–3058 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Meredith, R. J., Woods, R. J., Carmichael, I. & Serianni, A. S. Reconciling MA’AT and molecular dynamics models of linkage conformation in oligosaccharides. Phys. Chem. Chem. Phys. 22, 14454–14457 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang, W. et al. Does inter-residue hydrogen bonding in β-(1–>4)-linked disaccharides influence linkage conformation in aqueous solution? J. Phys. Chem. B 128, 2317–2325 (2024).

    Article  CAS  PubMed  Google Scholar 

  43. French, A. D., Montgomery, D. W., Prevost, N. T., Edwards, J. V. & Woods, R. J. Comparison of cellooligosaccharide conformations in complexes with proteins with energy maps for cellobiose. Carbohydr. Polym. 264, 118004 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kruskal, J. B. On the shortest spanning subtree of a graph and the traveling salesman problem. Proc. Am. Math. Soc. 7, 48–50 (1956).

    Article  Google Scholar 

  45. Nivedha, A. K., Makeneni, S., Foley, B. L., Tessier, M. B. & Woods, R. J. Importance of ligand conformational energies in carbohydrate docking: sorting the wheat from the chaff. J. Comput. Chem. 35, 526–539 (2014).

    Article  CAS  PubMed  Google Scholar 

  46. Case, D. A. et al. AmberTools. J. Chem. Inf. Model. 63, 6183–6191 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Roe, D. R. & Cheatham, T. E. III. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9, 3084–3095 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).

    Article  CAS  Google Scholar 

  49. Mahoney, M. W. & Jorgensen, W. L. A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions. J. Chem. Phys. 112, 8910–8922 (2000).

    Article  CAS  Google Scholar 

  50. Funcke, W., von Sonntag, C. & Triantaphylides, C. Detection of the open-chain forms of D-fructose and L-sorbose in aqueous solution by using 13C-n.m.r. spectroscopy. Carbohydr. Res. 75, 305–309 (1979).

    Article  CAS  Google Scholar 

  51. Jeffrey, G. A. & Huang, D.-b. The hydrogen bonding in the crystal structure of raffinose pentahydrate. Carbohydr. Res. 206, 173–182 (1990).

    Article  CAS  PubMed  Google Scholar 

  52. Beevers, C. A., McDonald, T. R. R., Robertson, J. H. & Stern, F. The crystal structure of sucrose. Acta Crystallogr. 5, 689–690 (1952).

    Article  CAS  Google Scholar 

  53. Wang, X. & Woods, R. J. Insights into furanose solution conformations: beyond the two-state model. J. Biomol. NMR 64, 291–305 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rao, V. S. R., Qasba, P. K., Balaji, P. V. & Chandrasekaran, R. Conformation of Carbohydrates (Harwood Academic Publishers, 1998).

  55. Makeneni, S., Foley, B. L. & Woods, R. J. BFMP: a method for discretizing and visualizing pyranose conformations. J. Chem. Inf. Model. 54, 2744–2750 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

R.J.W. thanks the National Institutes of Health (R24 GM136984, U01 CA207824, R01 GM100058, R01 AI155975 and P41 GM103390) and GlycoMIP, a National Science Foundation Materials Innovation Platform funded through Cooperative Agreement DMR-1933525 for supporting the development of GLYCAM-Web. D.S. acknowledges funding from the Grant Agency of Czech Republic JuniorStar project (22-30571M). X.W. acknowledges support from the Hubei Provincial Natural Science Foundation of China (2025AFB695).

Author information

Authors and Affiliations

  1. Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA

    Oliver C. Grant, Daniel Wentworth, Samuel G. Holmes, Rajan Kandel, Xiaocong Wang, Yao Xiao, Preston Sheppard, Tobias Grelsson, Andrew Coulter, Grayson Miller, Arunima Singh, Meenakshi Nagarajan, Bethany L. Foley & Robert J. Woods

  2. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic

    David Sehnal

  3. Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, China

    Xiaocong Wang

Authors
  1. Oliver C. Grant
    View author publications

    Search author on:PubMed Google Scholar

  2. Daniel Wentworth
    View author publications

    Search author on:PubMed Google Scholar

  3. Samuel G. Holmes
    View author publications

    Search author on:PubMed Google Scholar

  4. Rajan Kandel
    View author publications

    Search author on:PubMed Google Scholar

  5. David Sehnal
    View author publications

    Search author on:PubMed Google Scholar

  6. Xiaocong Wang
    View author publications

    Search author on:PubMed Google Scholar

  7. Yao Xiao
    View author publications

    Search author on:PubMed Google Scholar

  8. Preston Sheppard
    View author publications

    Search author on:PubMed Google Scholar

  9. Tobias Grelsson
    View author publications

    Search author on:PubMed Google Scholar

  10. Andrew Coulter
    View author publications

    Search author on:PubMed Google Scholar

  11. Grayson Miller
    View author publications

    Search author on:PubMed Google Scholar

  12. Arunima Singh
    View author publications

    Search author on:PubMed Google Scholar

  13. Meenakshi Nagarajan
    View author publications

    Search author on:PubMed Google Scholar

  14. Bethany L. Foley
    View author publications

    Search author on:PubMed Google Scholar

  15. Robert J. Woods
    View author publications

    Search author on:PubMed Google Scholar

Contributions

O.C.G developed the underlying scientific code, drafted and edited the paper. S.G.H. sourced literature data to determine default values and generated tables/figures. R.K. sourced the literature data, performed comparisons against experimental data and generated figures. D.S. provided guidance for the integration of Mol* onto the website. X.W. and A.S. generated GLYCAM parameters and prep files used by the website. Y.X., P.S, T.G., A.C, G.M, M.N. and B.L.F. developed the underlying scientific, website and cyberinfrastructure code. R.J.W. conceptualized GLYCAM-Web, guided its development and edited the paper.

Corresponding author

Correspondence to Robert J. Woods.

Ethics declarations

Competing interests

A.S. is currently employed as a Senior Editor for Nature Methods. She was not involved in the decision-making process for this paper and did not have access to confidential information pertaining to the peer review and editorial process. The other authors declare no competing interests.

Peer review

Peer review information

Nature Methods thanks Jon Agirre, Fiona Kearns and other, anonymous reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Primary Handling Editor: Allison Doerr, in collaboration with the Nature Methods team.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grant, O.C., Wentworth, D., Holmes, S.G. et al. Generating 3D models of complex carbohydrates with GLYCAM-Web. Nat Methods 23, 720–723 (2026). https://doi.org/10.1038/s41592-026-03033-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41592-026-03033-w

Search

Advanced search

Quick links

Nature Briefing AI and Robotics

Sign up for the Nature Briefing: AI and Robotics newsletter — what matters in AI and robotics research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: AI and Robotics