skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates

Abstract

Characterizing glycans and glycoconjugates in the context of three-dimensional structures is important in understanding their biological roles and developing efficient therapeutic agents. Computational modeling and molecular simulation have become an essential tool complementary to experimental methods. In this work, we present a computational tool, Glycan Modeler for in silico N–/O–glycosylation of the target protein and generation of carbohydrate-only systems. In our previous study, we developed Glycan Reader, a web-based tool for detecting carbohydrate molecules from a PDB structure and generation of simulation system and input files. As integrated into Glycan Reader in CHARMM-GUI, Glycan Modeler (Glycan Reader & Modeler) enables to generate the structures of glycans and glycoconjugates for given glycan sequences and glycosylation sites using PDB glycan template structures from Glycan Fragment Database (http://glycanstructure.org/fragment-db). Our benchmark tests demonstrate the universal applicability of Glycan Reader & Modeler to various glycan sequences and target proteins. We also investigated the structural properties of modeled glycan structures by running 2-μs molecular dynamics simulations of HIV envelope protein. The simulations show that the modeled glycan structures built by Glycan Reader & Modeler have the similar structural features compared to the ones solved by X-ray crystallography. We also describe the representative examples of glycoconjugate modelingmore » with video demos to illustrate the practical applications of Glycan Reader & Modeler. Glycan Reader & Modeler is freely available at http://charmm-gui.org/input/glycan.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [3];  [4];  [4];  [4];  [1]
  1. Lehigh Univ., Bethlehem, PA (United States)
  2. East China Normal Univ. (ECNU), Shanghai (China)
  3. Argonne National Lab. (ANL), Argonne, IL (United States)
  4. Korea Inst. for Advanced Study (Korea, Republic of)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Science Foundation (NSF); National Research Foundation of Korea (NRF); National Institutes of Health (NIH)
OSTI Identifier:
1559867
Grant/Contract Number:  
AC02-06CH11357; MCB070009; NRF-2017R1E1A1A01077717; P41GM103712-S1
Resource Type:
Accepted Manuscript
Journal Name:
Glycobiology
Additional Journal Information:
Journal Volume: 29; Journal Issue: 4
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Glycan Reader; N-linked glycosylation; O-linked glycosylation; molecular dynamics simulation; protein-glycan interaction; template-based glycan modeling

Citation Formats

Park, Sang-Jun, Lee, Jumin, Qi, Yifei, Kern, Nathan R., Lee, Hui Sun, Jo, Sunhwan, Joung, InSuk, Joo, Keehyung, Lee, Jooyoung, and Im, Wonpil. CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates. United States: N. p., 2019. Web. doi:10.1093/glycob/cwz003.
Park, Sang-Jun, Lee, Jumin, Qi, Yifei, Kern, Nathan R., Lee, Hui Sun, Jo, Sunhwan, Joung, InSuk, Joo, Keehyung, Lee, Jooyoung, & Im, Wonpil. CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates. United States. doi:10.1093/glycob/cwz003.
Park, Sang-Jun, Lee, Jumin, Qi, Yifei, Kern, Nathan R., Lee, Hui Sun, Jo, Sunhwan, Joung, InSuk, Joo, Keehyung, Lee, Jooyoung, and Im, Wonpil. Tue . "CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates". United States. doi:10.1093/glycob/cwz003. https://www.osti.gov/servlets/purl/1559867.
@article{osti_1559867,
title = {CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates},
author = {Park, Sang-Jun and Lee, Jumin and Qi, Yifei and Kern, Nathan R. and Lee, Hui Sun and Jo, Sunhwan and Joung, InSuk and Joo, Keehyung and Lee, Jooyoung and Im, Wonpil},
abstractNote = {Characterizing glycans and glycoconjugates in the context of three-dimensional structures is important in understanding their biological roles and developing efficient therapeutic agents. Computational modeling and molecular simulation have become an essential tool complementary to experimental methods. In this work, we present a computational tool, Glycan Modeler for in silico N–/O–glycosylation of the target protein and generation of carbohydrate-only systems. In our previous study, we developed Glycan Reader, a web-based tool for detecting carbohydrate molecules from a PDB structure and generation of simulation system and input files. As integrated into Glycan Reader in CHARMM-GUI, Glycan Modeler (Glycan Reader & Modeler) enables to generate the structures of glycans and glycoconjugates for given glycan sequences and glycosylation sites using PDB glycan template structures from Glycan Fragment Database (http://glycanstructure.org/fragment-db). Our benchmark tests demonstrate the universal applicability of Glycan Reader & Modeler to various glycan sequences and target proteins. We also investigated the structural properties of modeled glycan structures by running 2-μs molecular dynamics simulations of HIV envelope protein. The simulations show that the modeled glycan structures built by Glycan Reader & Modeler have the similar structural features compared to the ones solved by X-ray crystallography. We also describe the representative examples of glycoconjugate modeling with video demos to illustrate the practical applications of Glycan Reader & Modeler. Glycan Reader & Modeler is freely available at http://charmm-gui.org/input/glycan.},
doi = {10.1093/glycob/cwz003},
journal = {Glycobiology},
number = 4,
volume = 29,
place = {United States},
year = {2019},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share:

Works referenced in this record:

GENESIS: a hybrid-parallel and multi-scale molecular dynamics simulator with enhanced sampling algorithms for biomolecular and cellular simulations: GENESIS
journal, May 2015

  • Jung, Jaewoon; Mori, Takaharu; Kobayashi, Chigusa
  • Wiley Interdisciplinary Reviews: Computational Molecular Science, Vol. 5, Issue 4
  • DOI: 10.1002/wcms.1220

TM-align: a protein structure alignment algorithm based on the TM-score
journal, April 2005


Glycan fragment database: a database of PDB-based glycan 3D structures
journal, October 2012

  • Jo, Sunhwan; Im, Wonpil
  • Nucleic Acids Research, Vol. 41, Issue D1
  • DOI: 10.1093/nar/gks987

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience
journal, January 2017

  • Pérez, Serge; de Sanctis, Daniele
  • Beilstein Journal of Organic Chemistry, Vol. 13
  • DOI: 10.3762/bjoc.13.114

Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth
journal, May 2016


Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

CHARMM-GUI Nanodisc Builder for modeling and simulation of various nanodisc systems : CHARMM-GUI
journal, January 2019

  • Qi, Yifei; Lee, Jumin; Klauda, Jeffery B.
  • Journal of Computational Chemistry, Vol. 40, Issue 7
  • DOI: 10.1002/jcc.25773

GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation
journal, February 2008

  • Hess, Berk; Kutzner, Carsten; van der Spoel, David
  • Journal of Chemical Theory and Computation, Vol. 4, Issue 3
  • DOI: 10.1021/ct700301q

The Amber biomolecular simulation programs
journal, January 2005

  • Case, David A.; Cheatham, Thomas E.; Darden, Tom
  • Journal of Computational Chemistry, Vol. 26, Issue 16
  • DOI: 10.1002/jcc.20290

Cell surface biology mediated by low affinity multivalent protein–glycan interactions
journal, December 2004


On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database
journal, December 1999

  • Apweiler, Rolf; Hermjakob, Henning; Sharon, Nathan
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1473, Issue 1, p. 4-8
  • DOI: 10.1016/S0304-4165(99)00165-8

Symbol Nomenclature for Graphical Representations of Glycans
journal, November 2015

  • Varki, Ajit; Cummings, Richard D.; Aebi, Markus
  • Glycobiology, Vol. 25, Issue 12
  • DOI: 10.1093/glycob/cwv091

Fast Parallel Algorithms for Short-Range Molecular Dynamics
journal, March 1995


GLYCOSCIENCES.de: an Internet portal to support glycomics and glycobiology research
journal, May 2006

  • Lütteke, Thomas; Bohne-Lang, Andreas; Loss, Alexander
  • Glycobiology, Vol. 16, Issue 5
  • DOI: 10.1093/glycob/cwj049

doGlycans –Tools for Preparing Carbohydrate Structures for Atomistic Simulations of Glycoproteins, Glycolipids, and Carbohydrate Polymers for GROMACS
journal, October 2017

  • Danne, Reinis; Poojari, Chetan; Martinez-Seara, Hector
  • Journal of Chemical Information and Modeling, Vol. 57, Issue 10
  • DOI: 10.1021/acs.jcim.7b00237

Function and 3D Structure of the N-Glycans on Glycoproteins
journal, July 2012

  • Nagae, Masamichi; Yamaguchi, Yoshiki
  • International Journal of Molecular Sciences, Vol. 13, Issue 7
  • DOI: 10.3390/ijms13078398

Turning 'sweet' on immunity: galectin–glycan interactions in immune tolerance and inflammation
journal, May 2009

  • Rabinovich, Gabriel A.; Toscano, Marta A.
  • Nature Reviews Immunology, Vol. 9, Issue 5
  • DOI: 10.1038/nri2536

CHARMM-GUI Membrane Builder toward realistic biological membrane simulations
journal, August 2014

  • Wu, Emilia L.; Cheng, Xi; Jo, Sunhwan
  • Journal of Computational Chemistry, Vol. 35, Issue 27
  • DOI: 10.1002/jcc.23702

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation
journal, November 2012

  • Eastman, Peter; Friedrichs, Mark S.; Chodera, John D.
  • Journal of Chemical Theory and Computation, Vol. 9, Issue 1
  • DOI: 10.1021/ct300857j

Glycan reader: Automated sugar identification and simulation preparation for carbohydrates and glycoproteins
journal, August 2011

  • Jo, Sunhwan; Song, Kevin C.; Desaire, Heather
  • Journal of Computational Chemistry, Vol. 32, Issue 14
  • DOI: 10.1002/jcc.21886

Residue-centric modeling and design of saccharide and glycoconjugate structures
journal, November 2016

  • Labonte, Jason W.; Adolf-Bryfogle, Jared; Schief, William R.
  • Journal of Computational Chemistry, Vol. 38, Issue 5
  • DOI: 10.1002/jcc.24679

Constant pressure molecular dynamics simulation: The Langevin piston method
journal, September 1995

  • Feller, Scott E.; Zhang, Yuhong; Pastor, Richard W.
  • The Journal of Chemical Physics, Vol. 103, Issue 11
  • DOI: 10.1063/1.470648

SWEET - WWW-based rapid 3D construction of oligo- and polysaccharides
journal, September 1999


CHARMM: The biomolecular simulation program
journal, July 2009

  • Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.
  • Journal of Computational Chemistry, Vol. 30, Issue 10
  • DOI: 10.1002/jcc.21287

Glycosylation in Cellular Mechanisms of Health and Disease
journal, September 2006


Parallelization and improvements of the generalized born model with a simple sWitching function for modern graphics processors
journal, January 2016

  • Arthur, Evan J.; Brooks, Charles L.
  • Journal of Computational Chemistry, Vol. 37, Issue 10
  • DOI: 10.1002/jcc.24280

CHARMM36m: an improved force field for folded and intrinsically disordered proteins
journal, November 2016

  • Huang, Jing; Rauscher, Sarah; Nawrocki, Grzegorz
  • Nature Methods, Vol. 14, Issue 1
  • DOI: 10.1038/nmeth.4067

CHARMM-GUI Membrane Builder for Mixed Bilayers and Its Application to Yeast Membranes
journal, July 2009


Community-Based Network Study of Protein-Carbohydrate Interactions in Plant Lectins Using Glycan Array Data
journal, April 2014


Structure of a heparin-linked biologically active dimer of fibroblast growth factor
journal, June 1998

  • DiGabriele, Anna D.; Lax, Irit; Chen, Denise I.
  • Nature, Vol. 393, Issue 6687
  • DOI: 10.1038/31741

GLYCAM06: A generalizable biomolecular force field. Carbohydrates: GLYCAM06
journal, September 2007

  • Kirschner, Karl N.; Yongye, Austin B.; Tschampel, Sarah M.
  • Journal of Computational Chemistry, Vol. 29, Issue 4
  • DOI: 10.1002/jcc.20820

CHARMM-GUI Micelle Builder for Pure/Mixed Micelle and Protein/Micelle Complex Systems
journal, July 2013

  • Cheng, Xi; Jo, Sunhwan; Lee, Hui Sun
  • Journal of Chemical Information and Modeling, Vol. 53, Issue 8
  • DOI: 10.1021/ci4002684

GS-align for glycan structure alignment and similarity measurement
journal, April 2015


Structural Analysis of Glycans by NMR Chemical Shift Prediction
journal, March 2011

  • Lundborg, Magnus; Widmalm, Göran
  • Analytical Chemistry, Vol. 83, Issue 5
  • DOI: 10.1021/ac1032534

CarbBuilder: Software for building molecular models of complex oligo- and polysaccharide structures: Software for Building Molecular Models
journal, June 2016

  • Kuttel, Michelle M.; Ståhle, Jonas; Widmalm, Göran
  • Journal of Computational Chemistry, Vol. 37, Issue 22
  • DOI: 10.1002/jcc.24428

The S variant of human α 1 -antitrypsin, structure and implications for function and metabolism
journal, January 1989

  • Engh, Richard; Löbermann, Hartmut; Schneider, Monika
  • "Protein Engineering, Design and Selection", Vol. 2, Issue 6
  • DOI: 10.1093/protein/2.6.407

Conformational Studies of Oligosaccharides and Glycopeptides:  Complementarity of NMR, X-ray Crystallography, and Molecular Modelling
journal, February 2002

  • Wormald, Mark R.; Petrescu, Andrei J.; Pao, Ya-Lan
  • Chemical Reviews, Vol. 102, Issue 2
  • DOI: 10.1021/cr990368i

Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G
journal, May 2016


PBEQ-Solver for online visualization of electrostatic potential of biomolecules
journal, May 2008

  • Jo, Sunhwan; Vargyas, Miklos; Vasko-Szedlar, Judit
  • Nucleic Acids Research, Vol. 36, Issue suppl_2
  • DOI: 10.1093/nar/gkn314

The 1.25 Å resolution refinement of the cholera toxin B-pentamer: evidence of peptide backbone strain at the receptor-binding site
journal, October 1998

  • Merritt, Ethan A.; Kuhn, Peter; Sarfaty, Steve
  • Journal of Molecular Biology, Vol. 282, Issue 5
  • DOI: 10.1006/jmbi.1998.2076

Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure
journal, October 2013

  • Lippert, Ross A.; Predescu, Cristian; Ierardi, Douglas J.
  • The Journal of Chemical Physics, Vol. 139, Issue 16
  • DOI: 10.1063/1.4825247

GlyProt: in silico glycosylation of proteins
journal, July 2005

  • Bohne-Lang, A.; von der Lieth, C. -W.
  • Nucleic Acids Research, Vol. 33, Issue Web Server
  • DOI: 10.1093/nar/gki385

Glycobiology:  Toward Understanding the Function of Sugars
journal, January 1996


An improved OPLS-AA force field for carbohydrates
journal, October 2002

  • Kony, D.; Damm, W.; Stoll, S.
  • Journal of Computational Chemistry, Vol. 23, Issue 15
  • DOI: 10.1002/jcc.10139

New spherical-cutoff methods for long-range forces in macromolecular simulation
journal, July 1994

  • Steinbach, Peter J.; Brooks, Bernard R.
  • Journal of Computational Chemistry, Vol. 15, Issue 7
  • DOI: 10.1002/jcc.540150702

Glycans Confer Specificity to the Recognition of Ganglioside Receptors by Botulinum Neurotoxin A
journal, December 2016

  • Hamark, Christoffer; Berntsson, Ronnie P. -A.; Masuyer, Geoffrey
  • Journal of the American Chemical Society, Vol. 139, Issue 1
  • DOI: 10.1021/jacs.6b09534

CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field
journal, December 2015

  • Lee, Jumin; Cheng, Xi; Swails, Jason M.
  • Journal of Chemical Theory and Computation, Vol. 12, Issue 1
  • DOI: 10.1021/acs.jctc.5b00935

Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations
journal, September 2007


CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans
journal, November 2018

  • Lee, Jumin; Patel, Dhilon S.; Ståhle, Jonas
  • Journal of Chemical Theory and Computation, Vol. 15, Issue 1
  • DOI: 10.1021/acs.jctc.8b01066

Glycan Reader is improved to recognize most sugar types and chemical modifications in the Protein Data Bank
journal, June 2017


GROMOS 53A6 GLYC , an Improved GROMOS Force Field for Hexopyranose-Based Carbohydrates
journal, September 2012

  • Pol-Fachin, Laercio; Rusu, Victor H.; Verli, Hugo
  • Journal of Chemical Theory and Computation, Vol. 8, Issue 11
  • DOI: 10.1021/ct300479h

Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding
journal, October 2018


Effects of N-glycosylation on protein conformation and dynamics: Protein Data Bank analysis and molecular dynamics simulation study
journal, March 2015

  • Lee, Hui Sun; Qi, Yifei; Im, Wonpil
  • Scientific Reports, Vol. 5, Issue 1
  • DOI: 10.1038/srep08926

POLYS 2.0: An open source software package for building three-dimensional structures of polysaccharides: The POLYSaccharide Builder 2.0
journal, April 2014

  • Engelsen, Søren B.; Hansen, Peter I.; Pérez, Serge
  • Biopolymers, Vol. 101, Issue 7
  • DOI: 10.1002/bip.22449

CHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses
journal, August 2009

  • Guvench, Olgun; Hatcher, Elizabeth; Venable, Richard M.
  • Journal of Chemical Theory and Computation, Vol. 5, Issue 9
  • DOI: 10.1021/ct900242e

Structure, Conformation, and Dynamics of Bioactive Oligosaccharides:  Theoretical Approaches and Experimental Validations
journal, December 2000

  • Imberty, Anne; Pérez, Serge
  • Chemical Reviews, Vol. 100, Issue 12
  • DOI: 10.1021/cr990343j

Modulation of human endothelial cell proliferation and migration by fucoidan and heparin
journal, December 1998


Modifications of Glycans: Biological Significance and Therapeutic Opportunities
journal, December 2011

  • Muthana, Saddam M.; Campbell, Christopher T.; Gildersleeve, Jeffrey C.
  • ACS Chemical Biology, Vol. 7, Issue 1
  • DOI: 10.1021/cb2004466

Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson-Boltzmann equation
journal, June 1998


CHARMM-GUI HMMM Builder for Membrane Simulations with the Highly Mobile Membrane-Mimetic Model
journal, November 2015


A smooth particle mesh Ewald method
journal, November 1995

  • Essmann, Ulrich; Perera, Lalith; Berkowitz, Max L.
  • The Journal of Chemical Physics, Vol. 103, Issue 19
  • DOI: 10.1063/1.470117

Glycolipid function
journal, June 1987


Alcohols, ethers, carbohydrates, and related compounds. I. The MM4 force field for simple compounds
journal, September 2003

  • Allinger, Norman L.; Chen, Kuo-Hsiang; Lii, Jenn-Huei
  • Journal of Computational Chemistry, Vol. 24, Issue 12
  • DOI: 10.1002/jcc.10268

The recognition of glycans by protein receptors. Insights from NMR spectroscopy
journal, January 2018

  • Ardá, Ana; Jiménez-Barbero, Jesús
  • Chemical Communications, Vol. 54, Issue 38
  • DOI: 10.1039/C8CC01444B

VMD: Visual molecular dynamics
journal, February 1996


Restricted N-glycan Conformational Space in the PDB and Its Implication in Glycan Structure Modeling
journal, March 2013