Molecular docking of carbohydrate ligands to antibodies: Structural validation against crystal structures

Mark James Agostino, Cassandra Jene, Tristan Paul Boyle, Paul Allen Ramsland, Elizabeth Yuriev

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)

Abstract

Cell surface glycoproteins play vital roles in cellular homeostasis and disease. Antibody recognition of glycosylation on different cells and pathogens is critically important for immune surveillance. Conversely, adverse immune reactions resulting from anti body - carbohydrate interactions have been implicated in the development of autoimmune diseases and impact areas Such as xenotransplantation and cancer treatment. Understanding the nature of antibody-carbohydrate interactions and the method by which saccharides fit into antibody binding sites is important ill understanding the recognition process. In silico techniques offer attractive alternatives to experimental methods (X-ray crystallography and NMR) for the study of antibody-carbohydrate complexes. In particular, molecular docking provides information about protein-ligand interactions ill systems that are difficult to study with experimental techniques. Before molecular docking can be used to investigate antibody-carbohydrate complexes, validation of an appropriate docking method is required. In this study, four popular docking programs, Glide, AutoDock, GOLD, and FlexX, were assessed for their ability to accurately dock carbohydrates to antibodies. Comparison of top ranking poses with crystal structures highlighted the strengths and weaknesses of these programs. Rigid docking, in which the protein conformation remains static, and flexible docking, where both the protein and ligand are treated as flexible, were compared. This study has revealed that generally molecular docking of carbohydrates to antibodies has been performed best by Glide.
Original languageEnglish
Pages (from-to)2749 - 2760
Number of pages12
JournalJournal of Chemical Information and Modeling
Volume49
Issue number12
DOIs
Publication statusPublished - 2009

Cite this

@article{706905b4571f4438a565b53753777232,
title = "Molecular docking of carbohydrate ligands to antibodies: Structural validation against crystal structures",
abstract = "Cell surface glycoproteins play vital roles in cellular homeostasis and disease. Antibody recognition of glycosylation on different cells and pathogens is critically important for immune surveillance. Conversely, adverse immune reactions resulting from anti body - carbohydrate interactions have been implicated in the development of autoimmune diseases and impact areas Such as xenotransplantation and cancer treatment. Understanding the nature of antibody-carbohydrate interactions and the method by which saccharides fit into antibody binding sites is important ill understanding the recognition process. In silico techniques offer attractive alternatives to experimental methods (X-ray crystallography and NMR) for the study of antibody-carbohydrate complexes. In particular, molecular docking provides information about protein-ligand interactions ill systems that are difficult to study with experimental techniques. Before molecular docking can be used to investigate antibody-carbohydrate complexes, validation of an appropriate docking method is required. In this study, four popular docking programs, Glide, AutoDock, GOLD, and FlexX, were assessed for their ability to accurately dock carbohydrates to antibodies. Comparison of top ranking poses with crystal structures highlighted the strengths and weaknesses of these programs. Rigid docking, in which the protein conformation remains static, and flexible docking, where both the protein and ligand are treated as flexible, were compared. This study has revealed that generally molecular docking of carbohydrates to antibodies has been performed best by Glide.",
author = "Agostino, {Mark James} and Cassandra Jene and Boyle, {Tristan Paul} and Ramsland, {Paul Allen} and Elizabeth Yuriev",
year = "2009",
doi = "10.1021/ci900388a",
language = "English",
volume = "49",
pages = "2749 -- 2760",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "ACS Books",
number = "12",

}

Molecular docking of carbohydrate ligands to antibodies: Structural validation against crystal structures. / Agostino, Mark James; Jene, Cassandra; Boyle, Tristan Paul; Ramsland, Paul Allen; Yuriev, Elizabeth.

In: Journal of Chemical Information and Modeling, Vol. 49, No. 12, 2009, p. 2749 - 2760.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Molecular docking of carbohydrate ligands to antibodies: Structural validation against crystal structures

AU - Agostino, Mark James

AU - Jene, Cassandra

AU - Boyle, Tristan Paul

AU - Ramsland, Paul Allen

AU - Yuriev, Elizabeth

PY - 2009

Y1 - 2009

N2 - Cell surface glycoproteins play vital roles in cellular homeostasis and disease. Antibody recognition of glycosylation on different cells and pathogens is critically important for immune surveillance. Conversely, adverse immune reactions resulting from anti body - carbohydrate interactions have been implicated in the development of autoimmune diseases and impact areas Such as xenotransplantation and cancer treatment. Understanding the nature of antibody-carbohydrate interactions and the method by which saccharides fit into antibody binding sites is important ill understanding the recognition process. In silico techniques offer attractive alternatives to experimental methods (X-ray crystallography and NMR) for the study of antibody-carbohydrate complexes. In particular, molecular docking provides information about protein-ligand interactions ill systems that are difficult to study with experimental techniques. Before molecular docking can be used to investigate antibody-carbohydrate complexes, validation of an appropriate docking method is required. In this study, four popular docking programs, Glide, AutoDock, GOLD, and FlexX, were assessed for their ability to accurately dock carbohydrates to antibodies. Comparison of top ranking poses with crystal structures highlighted the strengths and weaknesses of these programs. Rigid docking, in which the protein conformation remains static, and flexible docking, where both the protein and ligand are treated as flexible, were compared. This study has revealed that generally molecular docking of carbohydrates to antibodies has been performed best by Glide.

AB - Cell surface glycoproteins play vital roles in cellular homeostasis and disease. Antibody recognition of glycosylation on different cells and pathogens is critically important for immune surveillance. Conversely, adverse immune reactions resulting from anti body - carbohydrate interactions have been implicated in the development of autoimmune diseases and impact areas Such as xenotransplantation and cancer treatment. Understanding the nature of antibody-carbohydrate interactions and the method by which saccharides fit into antibody binding sites is important ill understanding the recognition process. In silico techniques offer attractive alternatives to experimental methods (X-ray crystallography and NMR) for the study of antibody-carbohydrate complexes. In particular, molecular docking provides information about protein-ligand interactions ill systems that are difficult to study with experimental techniques. Before molecular docking can be used to investigate antibody-carbohydrate complexes, validation of an appropriate docking method is required. In this study, four popular docking programs, Glide, AutoDock, GOLD, and FlexX, were assessed for their ability to accurately dock carbohydrates to antibodies. Comparison of top ranking poses with crystal structures highlighted the strengths and weaknesses of these programs. Rigid docking, in which the protein conformation remains static, and flexible docking, where both the protein and ligand are treated as flexible, were compared. This study has revealed that generally molecular docking of carbohydrates to antibodies has been performed best by Glide.

UR - http://pubs.acs.org.ezproxy.lib.monash.edu.au/doi/full/10.1021/ci900388a

U2 - 10.1021/ci900388a

DO - 10.1021/ci900388a

M3 - Article

VL - 49

SP - 2749

EP - 2760

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

SN - 1549-9596

IS - 12

ER -