Beilstein Arch. 2023, 202346. https://doi.org/10.3762/bxiv.2023.46.v1
Published 27 Oct 2023
Glycosaminoglycan (GAG) research in the past few decades has been crucial for gaining insights into various physiological, pathological and therapeutic aspects mediated by the direct interactions between the GAG molecules and diverse proteins. The structural and functional heterogeneities of GAGs as well as their ability to bind specific proteins are determined by the sugar composition of the GAG, the size of the GAG chains, the degree and the pattern of sulfation. A deep understanding of the interactions in protein-GAG complexes is essential to explain their biological functions. In this study, the umbrella sampling approach is used to pull away a GAG ligand from the binding site and then pull it back in. We analyze the binding interactions between GAGs of three types (heparin, desulfated heparan sulfate and chondroitin sulfate) with three different proteins (basic fibroblast growth factor, acidic fibroblast growth factor and cathepsin K). The main focus of our study is to evaluate whether the umbrella sampling approach is able to reproduce experimentally obtained structures, and how useful it can be for getting a deeper understanding of GAG properties, especially protein recognition specificity and multipose binding. We find that the binding free eneergy landscape in the proximity of the GAG native binding pose is complex and implies the co-existance of several binding poses. The sliding of a GAG chain along a protein surface could be a potential mechanism of GAG particular sequence recognition by proteins.
Keywords: glycosaminoglycan; molecular docking; protein-glycosaminoglycan interaction specificity; RS-REMD; umbrella sampling
|Format: PDF||Size: 2.1 MB||Download|
When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:
Marcisz, M.; Sebastian, A.; Gaardløs, M.; Zacharias, M.; Samsonov, S. A. Beilstein Arch. 2023, 202346. doi:10.3762/bxiv.2023.46.v1
Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below.
Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Zotero.
© 2023 Marcisz et al.; licensee Beilstein-Institut.
This is an open access work licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-archives.org/xiv/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this work could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.