Glycosylator: a Python framework for the rapid modeling of glycans
Tóm tắt
Carbohydrates are a class of large and diverse biomolecules, ranging from a simple monosaccharide to large multi-branching glycan structures. The covalent linkage of a carbohydrate to the nitrogen atom of an asparagine, a process referred to as N-linked glycosylation, plays an important role in the physiology of many living organisms. Most software for glycan modeling on a personal desktop computer requires knowledge of molecular dynamics to interface with specialized programs such as CHARMM or AMBER. There are a number of popular web-based tools that are available for modeling glycans (e.g., GLYCAM-WEB (http://
https://dev.glycam.org/gp/
) or Glycosciences.db (
http://www.glycosciences.de/
)). However, these web-based tools are generally limited to a few canonical glycan conformations and do not allow the user to incorporate glycan modeling into their protein structure modeling workflow. Here, we present Glycosylator, a Python framework for the identification, modeling and modification of glycans in protein structure that can be used directly in a Python script through its application programming interface (API) or through its graphical user interface (GUI). The GUI provides a straightforward two-dimensional (2D) rendering of a glycoprotein that allows for a quick visual inspection of the glycosylation state of all the sequons on a protein structure. Modeled glycans can be further refined by a genetic algorithm for removing clashes and sampling alternative conformations. Glycosylator can also identify specific three-dimensional (3D) glycans on a protein structure using a library of predefined templates. Glycosylator was used to generate models of glycosylated protein without steric clashes. Since the molecular topology is based on the CHARMM force field, new complex sugar moieties can be generated without modifying the internals of the code. Glycosylator provides more functionality for analyzing and modeling glycans than any other available software or webserver at present. Glycosylator will be a valuable tool for the glycoinformatics and biomolecular modeling communities.
Tài liệu tham khảo
Apweiler R, Hermjakob H, Sharon N. On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim Biophys Acta, Gen Subj. 1999;1473:4–8.
Yan A, Lennarz WJ. Unraveling the mechanism of protein N-glycosylation. J Biol Chem. 2005;280:3121–4.
Spiro RG. Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptides bonds. Glycobiology. 2002;12:43R–56R.
Gavel Y, von Heijne G. Sequence differences between glycosylated and non-glycosylated Asn-X-Thr/Ser acceptor sites: implications for protein engineering. Protein Eng Des Sel. 1990;3:433–42.
Xu C, Ng DTW. Glycosylation-directed quality control of protein folding. Nat Rev Mol Cell Biol. 2015;16:742–52.
Ferreira IG, Pucci M, Venturi G, Malagolini N, Chiricolo M, Dall’Olio F. Glycosylation as a main regulator of growth and death factor receptors signaling. Int J Mol Sci. 2018;19:580. https://doi.org/10.3390/ijms19020580.
Janik ME, Lityńska A, Vereecken P. Cell migration—the role of integrin glycosylation. Biochim Biophys Acta Gen Subj. 2010;1800:545–55.
Dell A, Galadari A, Sastre F, Hitchen P. Similarities and differences in the glycosylation mechanisms in prokaryotes and eukaryotes. Int J Microbiol. 2010. https://doi.org/10.1155/2010/148178.
Zhu F, Wu H. Insights into bacterial protein glycosylation in human microbiota. Sci China Life Sci. 2016;59:11–8.
Tate MD, Job ER, Deng Y-M, Gunalan V, Maurer-Stroh S, Reading PC. Playing hide and seek: how glycosylation of the influenza virus hemagglutinin can modulate the immune response to infection. Viruses. 2014;6:1294–316.
Vigerust DJ, Shepherd VL. Virus glycosylation: role in virulence and immune interactions. Trends Microbiol. 2007;15:211–8.
Tsuchiya S, Aoki NP, Shinmachi D, Matsubara M, Yamada I, Aoki-Kinoshita KF, et al. Implementation of GlycanBuilder to draw a wide variety of ambiguous glycans. Carbohydr Res. 2017;445:104–16.
Engelsen SB, Cros S, Mackie W, Pérez S. A molecular builder for carbohydrates: application to polysaccharides and complex carbohydrates. Biopolymers. 1996;39:417–33.
Danne R, Poojari C, Martinez-Seara H, Rissanen S, Lolicato F, Róg T, et al. doGlycans–tools for preparing carbohydrate structures for atomistic simulations of glycoproteins, glycolipids, and carbohydrate polymers for GROMACS. J Chem Inf Model. 2017;57:2401–6.
Bohne A, Lang E, von der Lieth CW. SWEET - WWW-based rapid 3D construction of oligo- and polysaccharides. Bioinformatics. 1999;15:767–8.
GLYCAM. http://glycam.org/. Accessed 5 Mar 2019.
Jo S, Song KC, Desaire H, MacKerell AD, Im W. Glycan reader: automated sugar identification and simulation preparation for carbohydrates and glycoproteins. J Comput Chem. 2011;32:3135–41.
Park S-J, Lee J, Patel DS, Ma H, Lee HS, Jo S, et al. Glycan reader is improved to recognize most sugar types and chemical modifications in the protein data Bank. Bioinformatics. 2017;33:3051–7.
Park S-J, Lee J, Qi Y, Kern NR, Lee HS, Jo S, et al. CHARMM-GUI glycan modeler for modeling and simulation of carbohydrates and glycoconjugates. Glycobiology. 2019;29:320–31.
Böhm M, Bohne-Lang A, Frank M, Loss A, Rojas-Macias MA, Lütteke T. Glycosciences.DB: an annotated data collection linking glycomics and proteomics data (2018 update). Nucleic Acids Res. 2019;47(Database issue):D1195–201.
Kirschner KN, Yongye AB, Tschampel SM, Gonzalez-Outeirino J, Daniels CR, Foley BL, et al. GLYCAM06: A generalizable biomolecular force field. Carbohydrates. J Comput Chem. 2008;29:622–55.
Guvench O, Mallajosyula SS, Raman EP, Hatcher E, Vanommeslaeghe K, Foster TJ, et al. CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling. J Chem Theory Comput. 2011;7:3162–80.
Jo S, Kim T, Iyer VG, Im W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem. 2008;29:1859–65.
Lee J, Patel DS, Ståhle J, Park S-J, Kern NR, Kim S, et al. CHARMM-GUI membrane builder for complex biological membrane simulations with glycolipids and lipoglycans. J Chem Theory Comput. 2019;15:775–86.
Bakan A, Meireles LM, Bahar I. Prody: protein dynamics inferred from theory and experiments. Bioinformatics. 2011;27:1575–7.
Hagberg AA, Schult DA, Swart PJ. Exploring network structure, dynamics, and function using NetworkX, in Proceedings of the 7th Python in Science Conference (SciPy2008), Gäel Varoquaux, Travis Vaught, and Jarrod Millman (Eds), Pasadena; 2008. p. 11–5.
Hunter JD. Matplotlib: a 2D graphics environment. Comput Sci Eng. 2007;9:90–5.
Le Mercier P, Mariethoz J, Lascano-Maillard J, Bonnardel F, Imberty A, Ricard-Blum S, et al. A bioinformatics view of glycan–virus interactions. Viruses. 2019;11:374.
Schierbaum F. Comprehensive Glycoscience (From Chemistry to Systems Biology). By Johannis P. Kamerling (Editor-in-Chief), Geert-J. Boons, Yuan Ch. Lee, Akemi Suzuki, Naoyuki Taniguchi, Alphons G.J. Voragen. Starch - Stärke. 2008;60:48–9.
Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14:33–8.
Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, et al. Scalable molecular dynamics with NAMD. J Comput Chem. 2005;26:1781–802.
Lütteke T, von der Lieth C-W. pdb-care (PDB CArbohydrate REsidue check): A program to support annotation of complex carbohydrate structures in PDB files. BMC Bioinformatics. 2004;5:69.
Stewart-Jones GBE, Soto C, Lemmin T, Chuang G-Y, Druz A, Kong R, et al. Trimeric HIV-1-Env structures define glycan shields from clades a, B, and G. Cell. 2016;165:813–26.
Shahzad-Ul-Hussan S, Sastry M, Lemmin T, Soto C, Loesgen S, Scott DA, et al. Insights from NMR spectroscopy into the conformational properties of Man-9 and its recognition by two HIV binding proteins. Chembiochem. 2017;18:764–71.
Lemmin T, Soto C, Stuckey J, Kwong PD. Microsecond dynamics and network analysis of the HIV-1 SOSIP Env trimer reveal collective behavior and conserved microdomains of the glycan shield. Structure. 2017;25:1631–1639.e2.