Modeling large protein–glycosaminoglycan complexes using a fragment-based approach

Sergey A. Samsonov, Martin Zacharias, Isaure Chauvot de Beauchene

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Glycosaminoglycans (GAGs), a major constituent of the extracellular matrix, participate in cell-signaling by binding specific proteins. Structural data on protein–GAG interactions are crucial to understand and modulate these signaling processes, with potential applications in regenerative medicine. However, experimental and theoretical approaches used to study GAG–protein systems are challenged by GAGs high flexibility limiting the conformational sampling above a certain size, and by the scarcity of GAG-specific docking tools compared to protein–protein or protein–drug docking approaches. We present for the first time an automated fragment-based method for docking GAGs on a protein binding site. In this approach, trimeric GAG fragments are flexibly docked to the protein, assembled based on their spacial overlap, and refined by molecular dynamics. The method appeared more successful than the classical full-ligand approach for most of 13 tested complexes with known structure. The approach is particularly promising for docking of long GAG chains, which represents a bottleneck for classical docking approaches applied to these systems.

Original languageEnglish
Pages (from-to)1429-1439
Number of pages11
JournalJournal of Computational Chemistry
Volume40
Issue number14
DOIs
StatePublished - 30 May 2019
Externally publishedYes

Keywords

  • fragment-based docking
  • glycans modeling
  • glycosaminoglycans docking
  • glycosaminoglycans-protein complex

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