Glycan reader: Automated sugar identification and simulation preparation for carbohydrates and glycoproteins

Understanding how glycosylation affects protein structure, dynamics, and function is an emerging and challenging problem in biology. As a first step toward glycan modeling in the context of structural glycobiology, we have developed Glycan Reader and integrated it into the CHARMM‐GUI, http://www.charmm‐gui.org/input/glycan. Glycan Reader greatly simplifies the reading of PDB structure files containing glycans through (i) detection of carbohydrate molecules, (ii) automatic annotation of carbohydrates based on their three‐dimensional structures, (iii) recognition of glycosidic linkages between carbohydrates as well as N‐/O‐glycosidic linkages to proteins, and (iv) generation of inputs for the biomolecular simulation program CHARMM with the proper glycosidic linkage setup. In addition, Glycan Reader is linked to other functional modules in CHARMM‐GUI, allowing users to easily generate carbohydrate or glycoprotein molecular simulation systems in solution or membrane environments and visualize the electrostatic potential on glycoprotein surfaces. These tools are useful for studying the impact of glycosylation on protein structure and dynamics. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011

[1]  Laxmikant V. Kalé,et al.  Scalable molecular dynamics with NAMD , 2005, J. Comput. Chem..

[2]  Claus-Wilhelm von der Lieth,et al.  GlyProt: in silico glycosylation of proteins , 2005, Nucleic Acids Res..

[3]  W. Im,et al.  Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson-Boltzmann equation , 1998 .

[4]  Gerrit Groenhof,et al.  GROMACS: Fast, flexible, and free , 2005, J. Comput. Chem..

[5]  R Apweiler,et al.  On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. , 1999, Biochimica et biophysica acta.

[6]  Martin Frank,et al.  Data mining the protein data bank: automatic detection and assignment of carbohydrate structures. , 2004, Carbohydrate research.

[7]  P E Bourne,et al.  The Protein Data Bank. , 2002, Nucleic acids research.

[8]  J U Baenziger,et al.  The role of glycosylation in protein recognition. Warner-Lambert Parke-Davis Award lecture. , 1985, The American journal of pathology.

[9]  B. Honig,et al.  Classical electrostatics in biology and chemistry. , 1995, Science.

[10]  Taehoon Kim,et al.  CHARMM‐GUI: A web‐based graphical user interface for CHARMM , 2008, J. Comput. Chem..

[11]  G. Gregoriadis,et al.  The role of sialic acid in determining the survival of glycoproteins in the circulation. , 1971, The Journal of biological chemistry.

[12]  The Complex Carbohydrate Research Center of the University of Georgia , 2007, Plant Molecular Biology Reporter.

[13]  Alexander D. MacKerell,et al.  CHARMM Additive All-Atom Force Field for Glycosidic Linkages between Hexopyranoses. , 2009, Journal of chemical theory and computation.

[14]  W. Im,et al.  Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations , 2007, PloS one.

[15]  Jianpeng Ma,et al.  CHARMM: The biomolecular simulation program , 2009, J. Comput. Chem..

[16]  J. Michalski,et al.  Glycomics and mass spectrometry. , 2005, Current pharmaceutical design.

[17]  Zukang Feng,et al.  Ligand Depot: a data warehouse for ligands bound to macromolecules , 2004, Bioinform..

[18]  Claus-Wilhelm von der Lieth,et al.  GlycoMapsDB: a database of the accessible conformational space of glycosidic linkages , 2007, Nucleic Acids Res..

[19]  Martin Frank,et al.  Carbohydrate Structure Suite (CSS): analysis of carbohydrate 3D structures derived from the PDB , 2004, Nucleic Acids Res..

[20]  G. Wiederschain,et al.  Essentials of glycobiology , 2009, Biochemistry (Moscow).

[21]  Holger Gohlke,et al.  The Amber biomolecular simulation programs , 2005, J. Comput. Chem..

[22]  A. Varki,et al.  Biological roles of oligosaccharides: all of the theories are correct , 1993, Glycobiology.

[23]  Andreas Bohne,et al.  SWEET - WWW-based rapid 3D construction of oligo- and polysaccharides , 1999, Bioinform..

[24]  D. Beglov,et al.  Atomic Radii for Continuum Electrostatics Calculations Based on Molecular Dynamics Free Energy Simulations , 1997 .

[25]  J. Vanderleyden,et al.  Glycoproteins in prokaryotes , 1997, Archives of Microbiology.

[26]  Alexander D. MacKerell,et al.  CHARMM additive all-atom force field for glycosidic linkages in carbohydrates involving furanoses. , 2010, The journal of physical chemistry. B.

[27]  Alexander D. MacKerell,et al.  CHARMM additive all-atom force field for aldopentofuranoses, methyl-aldopentofuranosides, and fructofuranose. , 2009, The journal of physical chemistry. B.

[28]  Jeffery B. Klauda,et al.  CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes. , 2009, Biophysical journal.

[29]  Alexander D. MacKerell,et al.  Additive empirical force field for hexopyranose monosaccharides , 2008, J. Comput. Chem..

[30]  Alexander D. MacKerell,et al.  CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields , 2009, J. Comput. Chem..

[31]  Martin Frank,et al.  GLYCOSCIENCES.de: an Internet portal to support glycomics and glycobiology research. , 2006, Glycobiology.

[32]  R. Levy,et al.  Computer simulations with explicit solvent: recent progress in the thermodynamic decomposition of free energies and in modeling electrostatic effects. , 1998, Annual review of physical chemistry.

[33]  Pauline M Rudd,et al.  Sugar-mediated ligand-receptor interactions in the immune system. , 2004, Trends in biotechnology.

[34]  B. Roux.  Influence of the membrane potential on the free energy of an intrinsic protein. , 1997, Biophysical journal.