Studying specificity in protein – glycosaminoglycan recognition with umbrella sampling

In this study, the umbrella sampling (US) 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 was to evaluate whether the US 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 found that the binding free energy landscape in the proximity of the GAG native binding pose is complex and implies the co-existence 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. Beilstein J. Org. Chem. 2023, 19, 1933–1946. doi:10.3762/bjoc.19.144
Source: Beilstein Journal of Organic Chemistry - Category: Chemistry Authors: Tags: glycosaminoglycan molecular docking protein – glycosaminoglycan interaction specificity RS-REMD umbrella sampling Full Research Paper Source Type: research