CHARMM-GUIGlycan Modelerfor 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. Here, 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.

Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane

“…In this study, we selected the sequence with galactose linked to the α1-6 arm for Asn1158 in all chains. However, readers can use Glycan Reader & Modeler [25][26][27] in CHARMM-GUI to modify the glycan sequences and build structures according to their requirements.…”

Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 Protein-Protein Interaction

“…S1) in all N-glycosylation sites including Asn103 of ACE2 in PDB:2AJF. Glycan Reader & Modeler (30)(31)(32) in CHARMM-GUI was used to model N-glycan core pentasaccharide in all glycosylation sites using the templates from GFDB (33) (Glycan Fragment Database). To compare the receptorbinding affinity between RBD CoV1 and RBD CoV2 and to explore influences of N-glycans on binding affinity, we made four systems: S CoV1+G (RBD CoV1 -ACE2 with N-glycans), S CoV1-G (RBD CoV1 -ACE2 without N-glycans), S CoV2+G (RBD CoV2 -ACE2 with N-glycans), and S CoV2-G (RBD CoV2 -ACE2 without N-glycans).…”

Not all therapeutic antibody isotypes are equal: the case of IgM versus IgG in Pertuzumab and Trastuzumab

“…Missing residues in HER2 ECDs were built as loops using Modeller. Using CHARMM-GUI Glycan Reader & Modeller, 46 we modelled the N-glycosylation of the Cm1 domain on the Pertuzumab IgM hexamer model bound to HER2 ECDs. Monosialylated complex glycans (Fig.…”