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. 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.