Residue-Centric Modeling and Design of Saccharide and Glycoconjugate Structures

By Jason W. Labonte, Jared Adolf-Bryfogle, William R. Schief, Jeffrey J. Gray. 2016

46 citations recorded by the source corpus.

The RosettaCarbohydrate framework is a new tool for modeling a wide variety of saccharide and glycoconjugate structures. This report describes the development of the framework and highlights its applications. The framework integrates with established protocols within the Rosetta modeling and design suite, and it handles the vast complexity and variety of carbohydrate molecules, including branching and sugar modifications. To address challenges of sampling and scoring, RosettaCarbohydrate can sample glycosidic bonds, side‐chain conformations, and ring forms, and it utilizes a glycan‐specific term within its scoring function. Rosetta can work with standard PDB, GLYCAM, and GlycoWorkbench (.gws) file formats. Saccharide residue‐specific chemical information is stored internally, permitting glycoengineering and design. Carbohydrate‐specific applications described herein include virtual glycosylation, loop‐modeling of carbohydrates, and docking of glyco‐ligands to antibodies. Benchmarking data are presented and compared to other studies, demonstrating Rosetta's ability to predict glyco‐ligand binding. The framework expands the tools available to glycoscientists and engineers. © 2016 Wiley Periodicals, Inc.

Subfields: Molecular Biology, Organic Chemistry, Radiology, Nuclear Medicine and Imaging

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Xingjie Pan
2. Tanja Kortemme
3. Jared Adolf-Bryfogle
4. Jumin Lee
5. Frank DiMaio
6. William R. Schief
7. Wonpil Im
8. Yifei Qi

In Organic Chemistry

1. Tanja Kortemme

In Radiology, Nuclear Medicine and Imaging

1. Jared Adolf-Bryfogle
2. William R. Schief
3. Tanja Kortemme
4. Xingjie Pan

Citations in the corpus

• Recent advances in de novo protein design: Principles, methods, and applications (2021, background): “B , protein design scoring functions are generalized to model small molecules (132) and carbohydrates (131).”
• Automatically fixing errors in glycoprotein structures with Rosetta (2018, methodology): “This Rosetta glycan refinement protocol expands upon previous iterations (Labonte et al., 2017) by avoiding fitting stereochemically unfavorable glycan structures into sparse experimental data and instead yielding physically realistic geometries based on prior knowledge of saccharide chemical proper”
• CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates (2019, methodology): “To facilitate the computational modeling of glycans, standalone programs such as POLYS (Engelsen et al. 2014), doGlycans (Danne et al. 2017), CarbBuilder (Kuttel et al. 2016), and RosettaCarbohydrate (Labonte et al. 2017) have been developed.”