Principal Investigator
Robert J
Woods
Awardee Organization
University Of Georgia
United States
Fiscal Year
2018
Activity Code
U01
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 5U01CA207824-03
Tools to enable non-specialists to model glycoconjugates and glycan-protein interactions
To ensure the continued advancement of the life sciences, it is necessary that an understanding of the significance and functions of carbohydrates (glycans) in human health and disease be widely available to all researchers in the life sciences. Current knowledge of these aspects of human physiology is considerable, but much of it is only available to experts in the glycosciences. Recently, there have been considerable advances in techniques computer modeling of carbohydrates, particularly those of relevance to human physiology and especially with regard to their interactions with proteins. However, as with most fields of relevance to glycobiology, access to these techniques has remained limited because only experts have the technological skills necessary to use them. This project proposes to develop internet-based software and educational resources that are freely available to all and that are designed especially for use by researchers in the life sciences. The long-term goal of this project is to enrich the discovery of glyco-based technologies and procedures that promote human health and extend life. We propose to generate a suite of online tools, “Computational Glycosciences Portal” (CGP), designed specifically for use by biomedical researchers who are not specialists in glycobiology or in the computational sciences. The tools will be built on the GLYCAM-Web platform that already hosts several online tools widely used in the glycoscience community. Since the infrastructure for GLYCAM-Web has recently undergone significant upgrades, there is a solid technological base upon which to expand current capabilities and add new ones. In particular, we propose to implement established techniques as tools that will allow researchers to generate and analyze computer models of glycan-protein complexes, to predict the 3D structures of glycoproteins and glycolipids, and to validate the 3D models against experimental data. These tools will allow researchers to examine the origins of affinity in bound complexes, to better understand glycan array data, to investigate the transformative aspects of glycosylation, and to compare results of their studies to results from NMR experiments among others. But, most importantly, we will ensure that these tools are usable by researchers with general biomedical knowledge who are not necessarily conversant with glycobiology or the computational glycosciences. We will ensure this in two ways. One, we will consult with researchers in these fields to find out what they need from tools such as these. Wherever possible, we will construct the tools to reflect their advice. Two, also based on these consultations, we will generate high-quality, freely-available, online educational materials, designed for these researchers, that describe the tools and techniques.
Publications
- Zhao P, Praissman JL, Grant OC, Cai Y, Xiao T, Rosenbalm KE, Aoki K, Kellman BP, Bridger R, Barouch DH, Brindley MA, Lewis NE, Tiemeyer M, Chen B, Woods RJ, Wells L. Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor. Cell host & microbe. 2020 Oct 7;28(4):586-601.e6. Epub 2020 Aug 24. PMID: 32841605
- de Vries RP, Peng W, Grant OC, Thompson AJ, Zhu X, Bouwman KM, de la Pena ATT, van Breemen MJ, Ambepitiya Wickramasinghe IN, de Haan CAM, Yu W, McBride R, Sanders RW, Woods RJ, Verheije MH, Wilson IA, Paulson JC. Three mutations switch H7N9 influenza to human-type receptor specificity. PLoS pathogens. 2017 Jun 15;13(6):e1006390. doi: 10.1371/journal.ppat.1006390. eCollection 2017 Jun. PMID: 28617868
- Kim SY, Jin W, Sood A, Montgomery DW, Grant OC, Fuster MM, Fu L, Dordick JS, Woods RJ, Zhang F, Linhardt RJ. Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antiviral research. 2020 Sep;181:104873. Epub 2020 Jul 10. PMID: 32653452
- Makeneni S, Thieker DF, Woods RJ. Applying Pose Clustering and MD Simulations To Eliminate False Positives in Molecular Docking. Journal of chemical information and modeling. 2018 Mar 26;58(3):605-614. Epub 2018 Mar 9. PMID: 29431438
- Li X, Grant OC, Ito K, Wallace A, Wang S, Zhao P, Wells L, Lu S, Woods RJ, Sharp JS. Structural Analysis of the Glycosylated Intact HIV-1 gp120-b12 Antibody Complex Using Hydroxyl Radical Protein Footprinting. Biochemistry. 2017 Feb 21;56(7):957-970. Epub 2017 Feb 6. PMID: 28102671
- Overeem NJ, Hamming PHE, Grant OC, Di Iorio D, Tieke M, Bertolino MC, Li Z, Vos G, de Vries RP, Woods RJ, Tito NB, Boons GPH, van der Vries E, Huskens J. Hierarchical Multivalent Effects Control Influenza Host Specificity. ACS central science. 2020 Dec 23;6(12):2311-2318. Epub 2020 Nov 12. PMID: 33376792
- Zhao P, Praissman JL, Grant OC, Cai Y, Xiao T, Rosenbalm KE, Aoki K, Kellman BP, Bridger R, Barouch DH, Brindley MA, Lewis NE, Tiemeyer M, Chen B, Woods RJ, Wells L. Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor. bioRxiv : the preprint server for biology. 2020 Jul 24. PMID: 32743578
- Flowers SA, Grant OC, Woods RJ, Rebeck GW. O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain. Glycobiology. 2020 Jan 28;30(2):74-85. PMID: 31616924
- Sehnal D, Grant OC. Rapidly Display Glycan Symbols in 3D Structures: 3D-SNFG in LiteMol. Journal of proteome research. 2019 Feb 1;18(2):770-774. Epub 2018 Sep 19. PMID: 30179493
- Nemanichvili N, Tomris I, Turner HL, McBride R, Grant OC, van der Woude R, Aldosari MH, Pieters RJ, Woods RJ, Paulson JC, Boons GJ, Ward AB, Verheije MH, de Vries RP. Fluorescent Trimeric Hemagglutinins Reveal Multivalent Receptor Binding Properties. Journal of molecular biology. 2019 Feb 15;431(4):842-856. Epub 2018 Dec 29. PMID: 30597163
- De Leoz MLA, Simón-Manso Y, Woods RJ, Stein SE. Cross-Ring Fragmentation Patterns in the Tandem Mass Spectra of Underivatized Sialylated Oligosaccharides and Their Special Suitability for Spectrum Library Searching. Journal of the American Society for Mass Spectrometry. 2019 Mar;30(3):426-438. Epub 2018 Dec 18. PMID: 30565163
- Amon R, Grant OC, Leviatan Ben-Arye S, Makeneni S, Nivedha AK, Marshanski T, Norn C, Yu H, Glushka JN, Fleishman SJ, Chen X, Woods RJ, Padler-Karavani V. A combined computational-experimental approach to define the structural origin of antibody recognition of sialyl-Tn, a tumor-associated carbohydrate antigen. Scientific reports. 2018 Jul 17;8(1):10786. PMID: 30018351
- Meredith RJ, Woods RJ, Carmichael I, Serianni AS. Reconciling MA'AT and molecular dynamics models of linkage conformation in oligosaccharides. Physical chemistry chemical physics : PCCP. 2020 Jul 8;22(26):14454-14457. PMID: 32597425
- Tang M, Wang X, Gandhi NS, Foley BL, Burrage K, Woods RJ, Gu Y. Effect of hydroxylysine-O-glycosylation on the structure of type I collagen molecule: A computational study. Glycobiology. 2020 Sep 28;30(10):830-843. PMID: 32188979
- Olson LJ, Misra SK, Ishihara M, Battaile KP, Grant OC, Sood A, Woods RJ, Kim JP, Tiemeyer M, Ren G, Sharp JS, Dahms NM. Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor. Communications biology. 2020 Sep 9;3(1):498. PMID: 32908216
- Zhang W, Meredith R, Yoon MK, Wang X, Woods RJ, Carmichael I, Serianni AS. Synthesis and O-Glycosidic Linkage Conformational Analysis of 13C-Labeled Oligosaccharide Fragments of an Antifreeze Glycolipid. The Journal of organic chemistry. 2019 Feb 15;84(4):1706-1724. Epub 2019 Jan 29. PMID: 30624062
- Thieker DF, Xu Y, Chapla D, Nora C, Qiu H, Felix T, Wang L, Moremen KW, Liu J, Esko JD, Woods RJ. Downstream Products are Potent Inhibitors of the Heparan Sulfate 2-O-Sulfotransferase. Scientific reports. 2018 Aug 7;8(1):11832. PMID: 30087361
- Zhao Y, Yang JY, Thieker DF, Xu Y, Zong C, Boons GJ, Liu J, Woods RJ, Moremen KW, Amster IJ. A Traveling Wave Ion Mobility Spectrometry (TWIMS) Study of the Robo1-Heparan Sulfate Interaction. Journal of the American Society for Mass Spectrometry. 2018 Jun;29(6):1153-1165. Epub 2018 Mar 8. PMID: 29520710
- Singh A, Montgomery D, Xue X, Foley BL, Woods RJ. GAG Builder: a web-tool for modeling 3D structures of glycosaminoglycans. Glycobiology. 2019 Jul 1;29(7):515-518. PMID: 31034567
- Wang Z, Hsieh PH, Xu Y, Thieker D, Chai EJE, Xie S, Cooley B, Woods RJ, Chi L, Liu J. Synthesis of 3-O-Sulfated Oligosaccharides to Understand the Relationship between Structures and Functions of Heparan Sulfate. Journal of the American Chemical Society. 2017 Apr 12;139(14):5249-5256. Epub 2017 Apr 3. PMID: 28340300
- Woods RJ. Predicting the Structures of Glycans, Glycoproteins, and Their Complexes. Chemical reviews. 2018 Sep 12;118(17):8005-8024. Epub 2018 Aug 9. PMID: 30091597
- Yu J, Grant OC, Pett C, Strahl S, Stahl S, Woods RJ, Westerlind U. Induction of Antibodies Directed Against Branched Core O-Mannosyl Glycopeptides-Selectivity Complimentary to the ConA Lectin. Chemistry (Weinheim an der Bergstrasse, Germany). 2017 Mar 8;23(14):3466-3473. Epub 2017 Feb 16. PMID: 28079948
- French AD, Montgomery DW, Prevost NT, Edwards JV, Woods RJ. Comparison of cellooligosaccharide conformations in complexes with proteins with energy maps for cellobiose. Carbohydrate polymers. 2021 Jul 15;264:118004. Epub 2021 Apr 2. PMID: 33910736
- Grant OC, Xue X, Ra D, Khatamian A, Foley BL, Woods RJ. Gly-Spec: a webtool for predicting glycan specificity by integrating glycan array screening data and 3D structure. Glycobiology. 2016 Oct;26(10):1027-1028. PMID: 28120784
- Peng W, Bouwman KM, McBride R, Grant OC, Woods RJ, Verheije MH, Paulson JC, de Vries RP. Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation. Journal of virology. 2018 Apr 27;92. (10). Print 2018 May 15. PMID: 29491160
- Sheikh MO, Thieker D, Chalmers G, Schafer CM, Ishihara M, Azadi P, Woods RJ, Glushka JN, Bendiak B, Prestegard JH, West CM. O2 sensing-associated glycosylation exposes the F-box-combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases. The Journal of biological chemistry. 2017 Nov 17;292(46):18897-18915. Epub 2017 Sep 19. PMID: 28928219
- Sood A, Gerlits OO, Ji Y, Bovin NV, Coates L, Woods RJ. Defining the Specificity of Carbohydrate-Protein Interactions by Quantifying Functional Group Contributions. Journal of chemical information and modeling. 2018 Sep 24;58(9):1889-1901. Epub 2018 Aug 22. PMID: 30086239
- Hopper JTS, Ambrose S, Grant OC, Krumm SA, Allison TM, Degiacomi MT, Tully MD, Pritchard LK, Ozorowski G, Ward AB, Crispin M, Doores KJ, Woods RJ, Benesch JLP, Robinson CV, Struwe WB. The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans. Structure (London, England : 1993). 2017 May 2;25(5):773-782.e5. Epub 2017 Apr 20. PMID: 28434916
- Zhang W, Turney T, Meredith R, Pan Q, Sernau L, Wang X, Hu X, Woods RJ, Carmichael I, Serianni AS. Conformational Populations of β-(1→4) O-Glycosidic Linkages Using Redundant NMR J-Couplings and Circular Statistics. The journal of physical chemistry. B. 2017 Apr 13;121(14):3042-3058. Epub 2017 Mar 30. PMID: 28296420
- Grant OC, Montgomery D, Ito K, Woods RJ. Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition. Scientific reports. 2020 Sep 14;10(1):14991. PMID: 32929138
- Ji Y, White YJ, Hadden JA, Grant OC, Woods RJ. New insights into influenza A specificity: an evolution of paradigms. Current opinion in structural biology. 2017 Jun;44:219-231. Epub 2017 Jul 1. PMID: 28675835
- Peng W, de Vries RP, Grant OC, Thompson AJ, McBride R, Tsogtbaatar B, Lee PS, Razi N, Wilson IA, Woods RJ, Paulson JC. Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity. Cell host & microbe. 2017 Jan 11;21(1):23-34. Epub 2016 Dec 22. PMID: 28017661