DOI: 10.5061/dryad.zkh1893mr
title: Molecular dynamics simulation files for: a molecular machine efficiently drives glycosaminoglycan assembly and secretion for osteoarthritis therapy

description: Osteoarthritis (OA), the most prevalent form of arthritis, affects 500
 million people worldwide and is characterized by an irreversible loss of
 glycosaminoglycans (GAGs) at articular surfaces. Despite advances,
 preserving cartilage GAGs and controlling their turnover in living cells
 remain challenging. Based on the hypothesis that GAGs can interact with
 cationic molecules, we demonstrated a cost-effective strategy to increase
 human cartilage GAGs using a molecular machine hexadimethrine bromide
 (HDMBr). HDMBr promoted stem cell chondrogenesis by attracting
 pericellular GAGs and upregulating vesicle formation, leading to increased
 matrix secretion. Particularly, HDMBr promoted the assembly of chondroitin
 sulfate (CS) into highly concentrated condensates during intracellular
 trafficking, resulting in more efficient GAG secretion. HDMBr was then
 evaluated as a potential therapeutic in two animal models. In a rabbit
 model of large cartilage defects, HDMBr promoted the intrinsic
 regeneration of GAG-rich hyaline-like cartilage and improved tissue
 integration. In a rat OA model, low-dose HDMBr treatment increased
 cartilage thickness, supported cartilage matrix homeostasis, and improved
 the efficiency of cell-based therapy, evidently slowing OA progression
 compared to other tested clinical treatments. Overall, this study
 introduces a cost-effective GAG manipulation approach to cartilage repair
 and joint preservation, offering new insights into the mechanisms of
 cell-material interactions.
description: # Molecular dynamics simulation files for: **A molecular machine
 efficiently drives glycosaminoglycan assembly and secretion for
 osteoarthritis therapy**
 [https://doi.org/10.5061/dryad.zkh1893mr](https://doi.org/10.5061/dryad.zkh1893mr) ## Description of the data and file structure This folder contains molecular dynamics simulation files for the article: **A molecular machine efficiently drives glycosaminoglycan assembly and secretion for osteoarthritis therapy**. They were used for demonstrating the interactions between chondroitin sulfate (CS) and the cationic polymer hexadimethrine bromide (HDMBr).  Comments and requests could be addressed to: [hwoy@zju.edu.cn](mailto:hwoy@zju.edu.cn); [YishanChen@intl.zju.edu.cn](mailto:YishanChen@intl.zju.edu.cn). All material is free of use, but we would appreciate it if we could be told. ### Files and variables #### File: MD\_files\_CS-HDMBR.zip **Description:**  **5-5.pdb, 5-10.pdb, and 10-5.pdb** contain the structures of CS-HDMBr complexes after 200 ns simulations for systems with CS:HDMBr ratios of 5:5, 5:10, and 10:5, respectively (Fig. 4K). **nclust5-5.xvg, nclust5-10.xvg, and nclust10-5.xvg** contain the number of clusters over time for the CS-HDMBr systems with CS:HDMBr ratios of 5:5, 5:10, and 10:5, respectively (Fig. 4L). These files were generated using the GROMACS gmx clustsize tool, which analyzes cluster formation and evolution during the simulation. **energy5-5.xvg, energy5-10.xvg, and energy10-5.xvg** contain the interaction energies between CS and HDMBr over time for systems with CS:HDMBr ratios of 5:5, 5:10, and 10:5, respectively (Fig. S6G). These files were generated using the GROMACS gmx energy tool. The energy terms include: Coul-SR:HB-CS : Electrostatic interactions between CS and HDMBr. LJ-SR:HB-CS : Van der Waals interactions between CS and HDMBr.