Importance of IdoA and IdoA(2S) ring conformations in computational studies of glycosaminoglycan-protein interactions

详细信息    查看全文

• 作者：Sergey A. Samsonov ; M. Teresa Pisabarro
• 关键词：Iduronic acid derivatives ; Heparin ; Sugar ring conformation ; Molecular docking ; MM-GBSA free energy calculations
• 刊名：Carbohydrate Research
• 出版年：2013
• 出版时间：15 November, 2013
• 年：2013
• 卷：381
• 期：Complete
• 页码：133-137
• 全文大小：1714 K

文摘

Glycosaminoglycans (GAGs) interact with chemokines and growth factors in the extracellular matrix and, therefore, mediate cell communication processes. Heparin is one of the most studied GAGs, for which many experimental structures of its complexes with proteins are available. One of the monosaccharide components of heparin, sulfated iduronic acid (IdoA(2S)), is observed to adopt both ¹C₄ and ²S₀ ring conformations. Despite the biological relevance of the sugar ring conformations for heparin-protein interactions, it is very challenging to take into account the conformational space of IdoA(2S) sugar ring for computational studies. Therefore, instead of systematically analyzing several ring conformations, which represents a combinatorial problem for a periodic heparin molecule, often only one ring conformation is taken into account. Here, we use docking and molecular dynamics (MD) to estimate how crucial this assumption could be for the conclusions being made in computational studies of heparin-protein interactions. We show that both docking solutions and free energy calculations from MD simulations are significantly affected by the conformations adopted by IdoA and IdoA(2S) rings. Therefore, in the application of computational approaches to heparin-protein systems the ring conformations should be treated properly to avoid misleading conclusions.